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Cao LM, Qiu YZ, Li ZZ, Wang GR, Xiao Y, Luo HY, Liu B, Wu Q, Bu LL. Extracellular Vesicles: Hermes between cancers and lymph nodes. Cancer Lett 2025; 623:217735. [PMID: 40268131 DOI: 10.1016/j.canlet.2025.217735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 04/16/2025] [Accepted: 04/19/2025] [Indexed: 04/25/2025]
Abstract
Cancer is one of the main causes of death and a major obstacle to increasing life expectancy in all countries of the world. Lymph node metastasis (LNM) of in cancer patients indicates poor prognosis and it is an important indication to determine the therapeutic regime. Therefore, more attention should be given to the molecular mechanics of tumor lymphangiogenesis and LNM. Extracellular vesicles (EVs) are nanoscale cargo-bearing membrane vesicles that can serve as key mediators for the intercellular communication. Like Hermes, the messenger of the Greek gods, EVs can be secreted by tumor cells to regulate the LNM process. Many evidence has proved the clinical correlation between EVs and LNM in various cancer types. EVs plays an active role in the process of metastasis by expressing its connotative molecules, including proteins, nucleic acids, and metabolites. However, the clear role of EVs in the process of cancer LNM has not been thoroughly studied yet. In this review, we will summarize the clinical and mechanical findings of EVs regulating role on cancer LNM, and discuss the advanced modification of the research proposal. We propose the "PUMP" principle of EVs in LNM, including Preparation, Unleash, Migration, and Planting.
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Affiliation(s)
- Lei-Ming Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yu-Zhong Qiu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Guang-Rui Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yao Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Han-Yue Luo
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China; Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China; Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
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Gu C, ChenLiu Z, Wu Q, Tang D. ncRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets. Ann Surg Oncol 2025:10.1245/s10434-025-17368-9. [PMID: 40358781 DOI: 10.1245/s10434-025-17368-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.
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Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Zhenni ChenLiu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Qihang Wu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Xuzhou Medical University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Dalian Medical University, Dalian Medical University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China.
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Mafakheri A, Fathi F, Majidpoor J, Moayeri H, Mortezaee K. Secretory exosomes from modified immune cells against cancer. Med Oncol 2025; 42:159. [PMID: 40208472 DOI: 10.1007/s12032-025-02706-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Accepted: 03/30/2025] [Indexed: 04/11/2025]
Abstract
Extracellular vesicles (EVs) play significant roles in cancer progression through mediating inter/intra cellular communications within tumor microenvironment (TME). EVs are used as non-invasive diagnostic tools, drug delivery systems, and cancer vaccines, considering the anti-tumor potential, safety, biocompatibility and physiochemical stability of endogenous EVs. Modification of immune cells, either genetically or epigenetically, is a growing field of cancer research with the goal of enhancing efficacy of immunotherapy. This review focuses on the possibility of manipulating immune cells including dendritic cells (DCs), natural killer (NK) cells and T cells to secrete EVs that exert immune function either by activating immune responses or altering immune cell behavior to enhance anti-tumor efficacy, and discusses potential obstacles and recommendations for improved functionality of this therapeutic method.
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Affiliation(s)
- Asrin Mafakheri
- Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Fardin Fathi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
| | - Jamal Majidpoor
- Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Hasan Moayeri
- Department of General Surgery, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Keywan Mortezaee
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
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Gajate-Arenas M, Sirvent-Blanco C, García-Pérez O, Domínguez-de-Barros A, Piñero JE, Lorenzo-Morales J, Córdoba-Lanús E. miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19. Mol Med 2025; 31:102. [PMID: 40089674 PMCID: PMC11910857 DOI: 10.1186/s10020-025-01154-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 03/05/2025] [Indexed: 03/17/2025] Open
Abstract
MicroRNAs (miRNAs) are gene regulators essential for cell homeostasis, their alteration is related to a pathological state, including infectious diseases like COVID-19. Identifying an altered profile of circulating miRNAs in mild COVID-19 may enhance our knowledge of the pathogenesis of SARS-CoV-2 and the range of clinical phenotypes. In the present study, a miRNA screening was performed by Next Generation Sequencing (NGS), and the expression levels of 13 resulting miRNAs were validated through RT-qPCR in the serum of 40 mild cases compared to 29 non-infected individuals. An in-silico analysis was performed to detect target genes and their related pathways. From the validated miRNAs, miR-1246 (p < 0.001), miR-423-5p (p < 0.001), miR-21-5p (p = 0.005), miR-146a-5p (p < 0.001), miR-4508 (p = 0.001), miR-629-5p (p < 0.001), and miR-210-3p (p = 0.002) were found downregulated in infected individuals. Only miR-27a-5p was overexpressed in subjects with COVID-19 (p = 0.013) and associated with SARS-CoV-2 infection (p = 0.010). The KEGG pathways and GO analysis revealed that the differentially expressed miRNAs were related to viral processes or immunological pathways: miR-27a-5p acts on the TGF-beta pathway; miR-21-5p targets SMAD7, which is associated with the inflammatory response in the lung; miR-1246 acts on p53 pathway; and miR-4508 acts on ICAM2. In conclusion, the most relevant miRNAs, miR-27a-5p and miR-21-5p, were differently expressed in mild forms of COVID-19. The higher expression of miR-27a-5p observed in mild COVID-19 cases may suggest a protective effect against severe forms of the disease. Reduced expression of miR-21-5p may prevent pulmonary inflammation and the progression of fibrosis. The downregulation of miR-1246 and miR-4508 in mild COVID-19 cases may conduct the correct control of the infection. Moreover, miR-423-5p might be a suitable biomarker in the early stages of SARS-CoV-2 infection.
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Affiliation(s)
- Malena Gajate-Arenas
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Candela Sirvent-Blanco
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain
| | - Omar García-Pérez
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Angélica Domínguez-de-Barros
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - José E Piñero
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain
- Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología. Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, 38200, Spain
| | - Jacob Lorenzo-Morales
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain.
- Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología. Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, 38200, Spain.
| | - Elizabeth Córdoba-Lanús
- Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, La Laguna, Tenerife, 38029, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, 28029, Spain.
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Wang J, Lv ZY, Li P, Zhang Y, Li X, Shen DF. Lnc PVT1 facilitates TGF-β1-induced human cardiac fibroblast activation in vitro and ISO-induced myocardial fibrosis in vivo through regulating MYC. Mol Cell Biochem 2025; 480:1611-1625. [PMID: 38997507 DOI: 10.1007/s11010-024-05060-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 06/29/2024] [Indexed: 07/14/2024]
Abstract
Cardiac fibrosis is a commonly seen pathophysiological process in various cardiovascular disorders, such as coronary heart disorder, hypertension, and cardiomyopathy. Cardiac fibroblast trans-differentiation into myofibroblasts (MFs) is a key link in myocardial fibrosis. LncRNA PVT1 participates in fibrotic diseases in multiple organs; however, its role and mechanism in cardiac fibrosis remain largely unknown. Human cardiac fibroblasts (HCFs) were stimulated with TGF-β1 to induce myofibroblast; Immunofluorescent staining, Immunoblotting, and fluorescence in situ hybridization were used to detect the myofibroblasts phenotypes and lnc PVT1 expression. Cell biological phenotypes induced by lnc PVT1 knockdown or overexpression were detected by CCK-8, flow cytometry, and Immunoblotting. A mouse model of myocardial fibrosis was induced using isoproterenol (ISO), and the cardiac functions were examined by echocardiography measurements, cardiac tissues by H&E, and Masson trichrome staining. In this study, TGF-β1 induced HCF transformation into myofibroblasts, as manifested as significantly increased levels of α-SMA, vimentin, collagen I, and collagen III; the expression level of lnc PVT1 expression showed to be significantly increased by TGF-β1 stimulation. The protein levels of TGF-β1, TGFBR1, and TGFBR2 were also decreased by lnc PVT1 knockdown. Under TGF-β1 stimulation, lnc PVT1 knockdown decreased FN1, α-SMA, collagen I, and collagen III protein contents, inhibited HCF cell viability and enhanced cell apoptosis, and inhibited Smad2/3 phosphorylation. Lnc PVT1 positively regulated MYC expression with or without TGF-β1 stimulation; MYC overexpression in TGF-β1-stimulated HCFs significantly attenuated the effects of lnc PVT1 knockdown on HCF proliferation and trans-differentiation to MFs. In the ISO-induced myocardial fibrosis model, lnc PVT1 knockdown partially reduced fibrotic area, improved cardiac functions, and decreased the levels of fibrotic markers. In addition, lnc PVT1 knockdown decreased MYC and CDK4 levels but increased E-cadherin in mice heart tissues. lnc PVT1 is up-regulated in cardiac fibrosis and TGF-β1-stimulated HCFs. Lnc PVT1 knockdown partially ameliorates TGF-β1-induced HCF activation and trans-differentiation into MFs in vitro and ISO-induced myocardial fibrosis in vivo, potentially through interacting with MYC and up-regulating MYC.
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Affiliation(s)
- Juan Wang
- The Second Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, China
| | - Zhong-Yin Lv
- The Fifth Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, China
| | - Peng Li
- The Fifth Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, China
| | - Yin Zhang
- The Fifth Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, China
| | - Xia Li
- The Fifth Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, China.
- Department of Cardiology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumchi, 830001, Xinjiang, China.
| | - Di-Fei Shen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
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Corbett RJ, Kaufman RS, McQuaid SW, Vaksman Z, Phul S, Brown MA, Mason JL, Waszak SM, Zhang B, Zhong C, Desai H, Hausler R, Naqvi AS, Chroni A, Geng Z, Gonzalez EM, Zhu Y, Heath AP, Li M, Storm PB, Resnick AC, Maxwell KN, Cole KA, Waanders AJ, Bornhorst M, MacFarland SP, Rokita JL, Diskin SJ. Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric CNS tumors. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.02.04.25321499. [PMID: 39974082 PMCID: PMC11838646 DOI: 10.1101/2025.02.04.25321499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterized the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumor patients from the Pediatric Brain Tumor Atlas (PBTA). We identified germline P/LP variants in 24.2% (201/830) of patients and the majority (154/201) lacked clinical reporting of genetic tumor syndromes. Among P/LP carriers, 30.7% had putative somatic second hits or loss of function tumor alterations. Finally, we linked pathogenic germline variation with novel somatic events and patient survival to highlight the impact of germline variation on tumorigenesis and patient outcomes.
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Affiliation(s)
- Ryan J Corbett
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Rebecca S Kaufman
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Shelly W McQuaid
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
- Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Zalman Vaksman
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Saksham Phul
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Miguel A Brown
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Jennifer L Mason
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Sebastian M Waszak
- Laboratory of Computational Neuro-Oncology, Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Bo Zhang
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Chuwei Zhong
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Heena Desai
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ryan Hausler
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ammar S Naqvi
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Antonia Chroni
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Zhuangzhuang Geng
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Elizabeth M Gonzalez
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Yuankun Zhu
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Allison P Heath
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Marilyn Li
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Phillip B Storm
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Adam C Resnick
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Kara N Maxwell
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kristina A Cole
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Oncology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Angela J Waanders
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
- Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Miriam Bornhorst
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
- Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Suzanne P MacFarland
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Oncology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jo Lynne Rokita
- Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Sharon J Diskin
- Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Division of Oncology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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7
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Moni ZA, Hasan Z, Alam MS, Roy N, Islam F. Diagnostic and Prognostic Significance of Exosomes and Their Components in Patients With Cancers. Cancer Med 2025; 14:e70569. [PMID: 39757782 DOI: 10.1002/cam4.70569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 12/15/2024] [Accepted: 12/21/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND Cancer is the second leading cause of human mortality worldwide. Extracellular vesicles (EVs) from liquid biopsy samples are used in early cancer detection, characterization, and surveillance. Exosomes are a subset of EVs produced by all cells and present in all body fluids. They play an important role in the development of cancer because they are active transporters capable of carrying the contents of any type of cell. The objective of this review was to provide a brief overview of the clinical implication of exosomes or exosomal components in cancer diagnosis and prognosis. METHODS An extensive review of the current literature of exosomes and their components in cancer diagnosis and prognosis were carried out in the current study. RESULTS Tumor cells release exosomes that contribute to the formation of the pre-metastatic microenvironment, angiogenesis, invasion, and treatment resistance. On the contrary, tumor cells release more exosomes than normal cells, and these tumor-specific exosomes can carry the genomic and proteomic signature contents of the tumor cells, which can act as tools for the diagnosis and prognosis of patients with cancers. CONCLUSION This information may help clinicians to improve the management of cancer patients in clinical settings in the future.
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Affiliation(s)
- Zinnat Ara Moni
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Zahid Hasan
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Md Shaheen Alam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Nitai Roy
- Department of Biochemistry and Molecular Biology, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Farhadul Islam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
- School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia
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8
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Yu X, Zhang Y, Luo F, Zhou Q, Zhu L. The role of microRNAs in the gastric cancer tumor microenvironment. Mol Cancer 2024; 23:170. [PMID: 39164671 PMCID: PMC11334576 DOI: 10.1186/s12943-024-02084-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 08/13/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack of reliable early detection techniques, a majority of patients have a poor prognosis. Therefore, identifying new tumor biomarkers and therapeutic targets is essential. This review aims to provide fresh insights into enhancing the prognosis of patients with GC by summarizing the processes through which microRNAs (miRNAs) regulate the tumor microenvironment (TME) and highlighting their critical role in the TME. MAIN TEXT A comprehensive literature review was conducted by focusing on the interactions among tumor cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, and immune cells within the GC TME. The role of noncoding RNAs, known as miRNAs, in modulating the TME through various signaling pathways, cytokines, growth factors, and exosomes was specifically examined. Tumor formation, metastasis, and therapy in GC are significantly influenced by interactions within the TME. miRNAs regulate tumor progression by modulating these interactions through multiple signaling pathways, cytokines, growth factors, and exosomes. Dysregulation of miRNAs affects critical cellular processes such as cell proliferation, differentiation, angiogenesis, metastasis, and treatment resistance, contributing to the pathogenesis of GC. CONCLUSIONS miRNAs play a crucial role in the regulation of the GC TME, influencing tumor progression and patient prognosis. By understanding the mechanisms through which miRNAs control the TME, potential biomarkers and therapeutic targets can be identified to improve the prognosis of patients with GC.
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Affiliation(s)
- Xianzhe Yu
- Department of Medical Oncology, West China Hospital, Sichuan University, Sichuan Province, Cancer Center, Chengdu, 610041, People's Republic of China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, People's Republic of China
- Department of Gastrointestinal Surgery, Chengdu Second People's Hospital, Sichuan Province, No. 10 Qinyun Nan Street, Chengdu, 610041, People's Republic of China
| | - Yin Zhang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
- Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China
- Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Fengming Luo
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
- Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
- Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Qinghua Zhou
- Department of Medical Oncology, West China Hospital, Sichuan University, Sichuan Province, Cancer Center, Chengdu, 610041, People's Republic of China.
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, People's Republic of China.
| | - Lingling Zhu
- Department of Medical Oncology, West China Hospital, Sichuan University, Sichuan Province, Cancer Center, Chengdu, 610041, People's Republic of China.
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, People's Republic of China.
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9
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Bayat M, Sadri Nahand J. Exosomal miRNAs: the tumor's trojan horse in selective metastasis. Mol Cancer 2024; 23:167. [PMID: 39164756 PMCID: PMC11334467 DOI: 10.1186/s12943-024-02081-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 08/12/2024] [Indexed: 08/22/2024] Open
Abstract
Organs of future metastasis are not passive receivers of circulating tumor cells, but are instead selectively and actively modified by the primary tumor before metastatic spread has even occurred. Tumors orchestrate a pre-metastatic program by conditioning distant organs to create microenvironments that foster the survival and proliferation of tumor cells before their arrival, thereby establishing pre-metastatic niches. Primary tumor-derived exosomes modulate these pre-metastatic niches, generating a permissive environment that facilitates the homing and expansion of tumor cells. Moreover, microRNAs have emerged as a key component of exosomal cargo, serving not only to induce the formation of pre-metastatic niches but also to prime these sites for the arrival and colonization of specific secondary tumor populations. Against this backdrop, this review endeavors to elucidate the impact of tumor-derived exosomal microRNAs on the genesis of their individualized pre-metastatic niches, with a view towards identifying novel means of specifying cancer metastasis and exploiting this phenomenon for cancer immunotherapy.
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Affiliation(s)
- Mobina Bayat
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 15731, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 15731, Iran.
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10
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Zheng L, Li J, Li Y, Sun W, Ma L, Qu F, Tan W. Empowering Exosomes with Aptamers for Precision Theranostics. SMALL METHODS 2024:e2400551. [PMID: 38967170 DOI: 10.1002/smtd.202400551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/04/2024] [Indexed: 07/06/2024]
Abstract
As information messengers for cell-to-cell communication, exosomes, typically small membrane vesicles (30-150 nm), play an imperative role in the physiological and pathological processes of living systems. Accumulating studies have demonstrated that exosomes are potential biological candidates for theranostics, including liquid biopsy-based diagnosis and drug delivery. However, their clinical applications are hindered by several issues, especially their unspecific detection and insufficient targeting ability. How to upgrade the accuracy of exosome-based theranostics is being widely explored. Aptamers, benefitting from their admirable characteristics, are used as excellent molecular recognition elements to empower exosomes for precision theranostics. With high affinity against targets and easy site-specific modification, aptamers can be incorporated with platforms for the specific detection of exosomes, thus providing opportunities for advancing disease diagnostics. Furthermore, aptamers can be tailored and functionalized on exosomes to enable targeted therapeutics. Herein, this review emphasizes the empowering of exosomes by aptamers for precision theranostics. A brief introduction of exosomes and aptamers is provided, followed by a discussion of recent progress in aptamer-based exosome detection for disease diagnosis, and the emerging applications of aptamer-functionalized exosomes for targeted therapeutics. Finally, current challenges and opportunities in this research field are presented.
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Affiliation(s)
- Liyan Zheng
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/ Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China
| | - Jin Li
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Yingying Li
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/ Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China
| | - Weidi Sun
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/ Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China
| | - LeLe Ma
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Fengli Qu
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, 310024, China
| | - Weihong Tan
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, 310024, China
- Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
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11
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Maiyulan A, Matsumoto Y, Wang H, Murakami K, Toyozumi T, Otsuka R, Shiraishi T, Kinoshita K, Hu J, Iida S, Morishita H, Makiyama T, Nishioka Y, Kano M, Matsubara H. Hypoxia‑regulated exosomal miR‑185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis. Oncol Lett 2024; 28:334. [PMID: 38827568 PMCID: PMC11140231 DOI: 10.3892/ol.2024.14467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 04/18/2024] [Indexed: 06/04/2024] Open
Abstract
Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR-185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR-185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR-185 expression was then confirmed by reverse transcription-quantitative PCR. Patient background and prognosis were compared between high and low miR-185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR-185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR-185 in KYSE-960 and T.Tn cell culture media. Overexpression of miR-185 suppressed the migration, invasion and colony-forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR-185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR-185 levels were associated with cN and cStage, and could predict progression-free survival and disease-specific survival of patients with ESCC after initial treatment. In conclusion, miR-185 holds potential as a prognostic biomarker and therapeutic target in ESCC.
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Affiliation(s)
- Abula Maiyulan
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Yasunori Matsumoto
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Huan Wang
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Kentaro Murakami
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Takeshi Toyozumi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Ryota Otsuka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Tadashi Shiraishi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Kazuya Kinoshita
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Jie Hu
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Shinichiro Iida
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Hiroki Morishita
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Tenshi Makiyama
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Yuri Nishioka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Masayuki Kano
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
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12
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Skryabin GO, Beliaeva AA, Enikeev AD, Tchevkina EM. Extracellular Vesicle miRNAs in Diagnostics of Gastric Cancer. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:1211-1238. [PMID: 39218020 DOI: 10.1134/s0006297924070058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/24/2024] [Accepted: 05/30/2024] [Indexed: 09/04/2024]
Abstract
Gastric cancer (GC) poses a significant global health challenge because of its high mortality rate attributed to the late-stage diagnosis and lack of early symptoms. Early cancer diagnostics is crucial for improving the survival rates in GC patients, which emphasizes the importance of identifying GC markers for liquid biopsy. The review discusses a potential use of extracellular vesicle microRNAs (EV miRNAs) as biomarkers for the diagnostics and prognostics of GC. Methods. Original articles on the identification of EV miRNA as GC markers published in the Web of Science and Scopus indexed issues were selected from the PubMed and Google Scholar databases. We focused on the methodological aspects of EV analysis, including the choice of body fluid, methods for EV isolation and validation, and approaches for EV miRNA analysis. Conclusions. Out of 33 found articles, the majority of authors investigated blood-derived extracellular vesicles (EVs); only a few utilized EVs from other body fluids, including tissue-specific local biofluids (washing the tumor growth areas), which may be a promising source of EVs in the context of cancer diagnostics. GC-associated miRNAs identified in different studies using different methods of EV isolation and analysis varied considerably. However, three miRNAs (miR-10b, miR-21, and miR-92a) have been found in several independent studies and shown to be associated with GC in experimental models. Further studies are needed to determine the optimal miRNA marker panel. Another essential step necessary to improve the reliability and reproducibility of EV-based diagnostics is standardization of methodologies for EV handling and analysis of EV miRNA.
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Affiliation(s)
- Gleb O Skryabin
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia.
| | - Anastasiya A Beliaeva
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
| | - Adel D Enikeev
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
| | - Elena M Tchevkina
- Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115522, Russia
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13
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Mao L, Liu S, Chen Y, Huang H, Ding F, Deng L. Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy. Front Cardiovasc Med 2024; 11:1399738. [PMID: 39006168 PMCID: PMC11239395 DOI: 10.3389/fcvm.2024.1399738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 06/14/2024] [Indexed: 07/16/2024] Open
Abstract
Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.
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Affiliation(s)
- Lixia Mao
- Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Songtao Liu
- Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yongxia Chen
- Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Huiyi Huang
- Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Fenghua Ding
- Outpatient Appointment Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Liehua Deng
- Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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14
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Liu M, Wen Z, Zhang T, Zhang L, Liu X, Wang M. The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis. Front Immunol 2024; 15:1417758. [PMID: 38983854 PMCID: PMC11231912 DOI: 10.3389/fimmu.2024.1417758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/12/2024] [Indexed: 07/11/2024] Open
Abstract
Exosomes represent a type of extracellular vesicles derived from the endosomal pathway that transport diverse molecular cargoes such as proteins, lipids, and nucleic acids. These cargoes have emerged as crucial elements impacting disease diagnosis, treatment, and prognosis, and are integral to the process of exosome formation. This review delves into the essential molecular cargoes implicated in the phases of exosome production and release. Emphasis is placed on their significance as cancer biomarkers and potential therapeutic targets, accompanied by an exploration of the obstacles and feasible applications linked to these developments.
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Affiliation(s)
- Meijin Liu
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Zhenzhen Wen
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Tingting Zhang
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Linghan Zhang
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Xiaoyan Liu
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Maoyuan Wang
- Laboratory Medicine, People's Hospital of Ganzhou Economic Development Zone, Ganzhou, China
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Gannan Medical University, GanZhou, China
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15
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Rizwan M, Mahjabeen I, Ashraf NS, Arshad M, Haris MS, Kayani MA. Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients. Future Oncol 2024; 20:1479-1493. [PMID: 38861304 PMCID: PMC11441060 DOI: 10.1080/14796694.2024.2351355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 05/01/2024] [Indexed: 06/12/2024] Open
Abstract
Aim: The present study aimed to figure out the potential role of exosomal microRNAs, and their targeted genes in HNC detection/diagnosis.Methods: In the present study, exosomes were extracted from the serum samples of 400 HNC patients and 400 healthy controls. Exosomes were characterized using TEM, NTA, TEM-immunogold labeling and ELISA. Quantitative PCR was used to measure the expression level of exosomal miRNA-19a, miRNA-19b and targeted genes SMAD2 and SMAD4 in HNC patients and controls.Results: The deregulation of miR-19a (p < 0.01), miR-19b (p < 0.03), SMAD2 (p < 0.04) and SMAD4 (p < 0.04) was observed in HNC patients vs controls.Conclusion: ROC curve and Kaplan-Meier analysis showed the good diagnostic/prognostic value of selected exosomal microRNAs and related genes in HNC patients.
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Affiliation(s)
- Muhammad Rizwan
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
| | - Ishrat Mahjabeen
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
| | - Nida Sarosh Ashraf
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
| | - Maryam Arshad
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
| | - Muhammad Shahbaz Haris
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
| | - Mahmood Akhtar Kayani
- Cancer Genetics & Epigenetics research group, Department of Biosciences, COMSATS University, Park Road Islamabad, Pakistan
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16
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Yang P, Lei H, Fu Y, Chen C, Tang L, Xia S, Guo Y, Chen G, Xie M, Yang J, Li F, Li L. Exosomal miR-151-3p in saliva: A potential non-invasive marker for gastric cancer diagnosis and prognosis modulated by Sijunzi decoction (SJZD) in mice. Heliyon 2024; 10:e29169. [PMID: 38633631 PMCID: PMC11021977 DOI: 10.1016/j.heliyon.2024.e29169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/19/2024] Open
Abstract
Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.
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Affiliation(s)
- Ping Yang
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Huijun Lei
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Yue Fu
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Cheng Chen
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Li Tang
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Shuaishuai Xia
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Yan Guo
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Guangyu Chen
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Mengzhou Xie
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
| | - Jingjing Yang
- Community Health Service Center of Dongtang Street, Yuhua District, Changsha, Hunan, 410004, China
| | - Feng Li
- School of Dentistry, University of California, Los Angeles, Los Angeles, CA90095, United States
| | - Liang Li
- Department of Chinese and Western Integrative Medicine, Hunan Brain Hospital, Clinical Medical School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation & Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China
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17
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Guan XL, Guan XY, Zhang ZY. Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer. World J Gastrointest Oncol 2024; 16:630-642. [PMID: 38577463 PMCID: PMC10989387 DOI: 10.4251/wjgo.v16.i3.630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 12/18/2023] [Accepted: 01/15/2024] [Indexed: 03/12/2024] Open
Abstract
As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.
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Affiliation(s)
- Xiao-Li Guan
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Xiao-Ying Guan
- Department of Pathology, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Zheng-Yi Zhang
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
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18
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Lei Y, Cai S, Zhang CD, Li YS. The biological role of extracellular vesicles in gastric cancer metastasis. Front Cell Dev Biol 2024; 12:1323348. [PMID: 38333593 PMCID: PMC10850573 DOI: 10.3389/fcell.2024.1323348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 01/15/2024] [Indexed: 02/10/2024] Open
Abstract
Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.
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Affiliation(s)
- Yun Lei
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shuang Cai
- Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Chun-Dong Zhang
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yong-Shuang Li
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
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19
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Beaumont JEJ, Ju J, Barbeau LMO, Demers I, Savelkouls KG, Derks K, Bouwman FG, Wauben MHM, Zonneveld MI, Keulers TGH, Rouschop KMA. GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development. Radiother Oncol 2024; 190:109968. [PMID: 37898438 DOI: 10.1016/j.radonc.2023.109968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/04/2023] [Accepted: 10/22/2023] [Indexed: 10/30/2023]
Abstract
BACKGROUND AND PURPOSE Hypoxia is a common feature of tumours, associated with poor prognosis due to increased resistance to radio- and chemotherapy and enhanced metastasis development. Previously we demonstrated that GABARAPL1 is required for the secretion of extracellular vesicles (EV) with pro-angiogenic properties during hypoxia. Here, we explored the role of GABARAPL1+ EV in the metastatic cascade. MATERIALS AND METHODS GABARAPL1 deficient or control MDA-MB-231 cells were injected in murine mammary fat pads. Lungs were dissected and analysed for human cytokeratin 18. EV from control and GABARAPL1 deficient cells exposed to normoxia (21% O2) or hypoxia (O2 < 0.02%) were isolated and analysed by immunoblot, nanoparticle tracking analysis, high resolution flow cytometry, mass spectrometry and next-generation sequencing. Cellular migration and invasion were analysed using scratch assays and transwell-invasion assays, respectively. RESULTS The number of pulmonary metastases derived from GABARAPL1 deficient tumours decreased by 84%. GABARAPL1 deficient cells migrate slower but display a comparable invasive capacity. Both normoxic and hypoxic EV contain proteins and miRNAs associated with metastasis development and, in line, increase cancer cell invasiveness. Although GABARAPL1 deficiency alters EV content, it does not alter the EV-induced increase in cancer cell invasiveness. CONCLUSION GABARAPL1 is essential for metastasis development. This is unrelated to changes in migration and invasion and suggests that GABARAPL1 or GABARAPL1+ EV are essential in other processes related to the metastatic cascade.
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Affiliation(s)
- Joel E J Beaumont
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Jinzhe Ju
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Lydie M O Barbeau
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Imke Demers
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Pathology, GROW-School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Kim G Savelkouls
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Kasper Derks
- Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Freek G Bouwman
- Department of Human Biology, NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marca H M Wauben
- Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Marijke I Zonneveld
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Tom G H Keulers
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Kasper M A Rouschop
- Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
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20
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Wu C, Li D, Cheng X, Gu H, Qian Y, Feng L. Downregulation of cancer-associated fibroblast exosome-derived miR-29b-1-5p restrains vasculogenic mimicry and apoptosis while accelerating migration and invasion of gastric cancer cells via immunoglobulin domain-containing 1/zonula occluden-1 axis. Cell Cycle 2023; 22:1807-1826. [PMID: 37587724 PMCID: PMC10599179 DOI: 10.1080/15384101.2023.2231740] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 11/01/2022] [Accepted: 05/02/2023] [Indexed: 08/18/2023] Open
Abstract
Background: Cancer-associated fibroblast (CAF) exosomal miRNAs have gradually a hot spot in cancer therapy. This study mainly explores the effect of CAF-derived exosomal miR-29b-1-5p on gastric cancer (GC) cells.Methods: CAFs and exosomes were identified by Western blot and transmission electron microscopy. CAF-derived exosomes-GC cells co-culture systems were constructed. Effects of CAF-derived exosomal miR-29b-1-5p on GC cells were determined by cell counting kit-8, flow cytometry, wound healing, Transwell assays and Western blot. The relationship between miR-29b-1-5p and immunoglobulin domain-containing 1 (VSIG1) was assessed by TargetScan, dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. The interaction between VSIG1 and zonula occluden-1 (ZO-1) was detected by co-immunoprecipitation. Expressions of miR-29b-1-5p, VSIG1 and ZO-1 were determined by quantitative real-time PCR. Vascular mimicry (VM) was detected using immunohistochemistry and tube formation assays. Rescue experiments and xenograft tumor assays were used to further determine the effect of CAF-derived exosomal miR-29b-1-5p/VSIG1 on GC.Results: VM structure, upregulation of miR-29b-1-5p, and downregulation of VSIG1 and ZO-1 were shown in GC tissues. MiR-29b-1-5p targeted VSIG1, which interacted with ZO-1. CAF-derived exosomal miR-29b-1-5p inhibitor suppressed the viability, migration, invasion and VM formation, but promoted the apoptosis of GC cells. MiR-29b-1-5p inhibitor increased levels of VSIG1, ZO-1 and E-cadherin, whilst decreasing levels of VE-cadherin, N-cadherin and Vimentin in vitro and in vivo, which however was partially reversed by shVSIG1. Downregulation of CAF-derived exosomal miR-29b-1-5p impeded GC tumorigenesis and VM structure in vivo by upregulating VSIG1/ZO-1 expression.Conclusion: Downregulation of CAF-derived exosomal miR-29b-1-5p inhibits GC progression via VSIG1/ZO-1 axis.
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Affiliation(s)
- Chenqu Wu
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
| | - Deming Li
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
| | - Xun Cheng
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
| | - Hao Gu
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
| | - Yanqing Qian
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
| | - Li Feng
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
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21
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Logozzi M, Orefice NS, Di Raimo R, Mizzoni D, Fais S. The Importance of Detecting, Quantifying, and Characterizing Exosomes as a New Diagnostic/Prognostic Approach for Tumor Patients. Cancers (Basel) 2023; 15:cancers15112878. [PMID: 37296842 DOI: 10.3390/cancers15112878] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/11/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Exosomes are extracellular vesicles (EVs) of nanometric size studied for their role in tumor pathogenesis and progression and as a new source of tumor biomarkers. The clinical studies have provided encouraging but probably unexpected results, including the exosome plasmatic levels' clinical relevance and well-known biomarkers' overexpression on the circulating EVs. The technical approach to obtaining EVs includes methods to physically purify EVs and characterize EVs, such as Nanosight Tracking Analysis (NTA), immunocapture-based ELISA, and nano-scale flow cytometry. Based on the above approaches, some clinical investigations have been performed on patients with different tumors, providing exciting and promising results. Here we emphasize data showing that exosome plasmatic levels are consistently higher in tumor patients than in controls and that plasmatic exosomes express well-known tumor markers (e.g., PSA and CEA), proteins with enzymatic activity, and nucleic acids. However, we also know that tumor microenvironment acidity is a key factor in influencing both the amount and the characteristics of the exosome released by tumor cells. In fact, acidity significantly increases exosome release by tumor cells, which correlates with the number of exosomes that circulate through the body of a tumor patient.
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Affiliation(s)
- Mariantonia Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Nicola Salvatore Orefice
- Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | | | - Davide Mizzoni
- ExoLab Italia, Tecnopolo d'Abruzzo, 67100 L'Aquila, Italy
| | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
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22
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Implications of Crosstalk between Exosome-Mediated Ferroptosis and Diseases for Pathogenesis and Treatment. Cells 2023; 12:cells12020311. [PMID: 36672245 PMCID: PMC9856458 DOI: 10.3390/cells12020311] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/04/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
Ferroptosis is a type of iron-dependent cell death caused by ferrous iron overload, reactive oxygen species generation through the Fenton reaction, and lipid peroxidation, leading to antioxidative system dysfunction and, ultimately, cell membrane damage. The functional role of ferroptosis in human physiology and pathology is considered a cause or consequence of diseases. Circulating exosomes mediate intercellular communication and organ crosstalk. They not only transport functional proteins and nucleic acids derived from parental cells but also serve as vehicles for the targeted delivery of exogenous cargo. Exosomes regulate ferroptosis by delivering the biological material to the recipient cell, affecting ferroptosis-related proteins, or transporting ferritin-bound iron out of the cell. This review discusses pathogenesis mediated by endogenous exosomes and the therapeutic potential of exogenous exosomes for ferroptosis-related diseases. In addition, this review explores the role of exosome-mediated ferroptosis in ferroptosis-related diseases with an emphasis on strategies for engineering exosomes for ferroptosis therapy.
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23
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Xu XH, Shao SL, Guo D, Ge LN, Wang Z, Liu P, Tao YY. Roles of microRNAs and exosomes in Helicobacter pylori associated gastric cancer. Mol Biol Rep 2023; 50:889-897. [PMID: 36367659 DOI: 10.1007/s11033-022-08073-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 10/30/2022] [Indexed: 11/13/2022]
Abstract
Helicobacter pylori (H. pylori) is a common pathogen that infects more than half of the world's population. Its infection can not only lead to a variety of gastrointestinal diseases, such as chronic gastritis and gastric cancer (GC) but also be associated with many extra-gastrointestinal diseases. Exosomes, as a new intercellular information transmission medium, can carry biological signal molecules such as microRNAs (miRNAs) to regulate a variety of cellular physiological activities and are involved in multiple cancer processes. In this article, we provide a systematic review on the role of exosomal miRNAs in H. pylori-associated GC.
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Affiliation(s)
- Xiao-Han Xu
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China
| | - Shu-Li Shao
- Department of Central Lab, Weihai Municipal Hospital, Weihai, Shandong, 264200, People's Republic of China
| | - Dong Guo
- Department of Central Lab, Weihai Municipal Hospital, Weihai, Shandong, 264200, People's Republic of China
| | - Li-Na Ge
- School of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning, 116044, People's Republic of China
| | - Zan Wang
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China
| | - Peng Liu
- Department of Central Lab, Weihai Municipal Hospital, Weihai, Shandong, 264200, People's Republic of China
| | - Yuan-Yong Tao
- Department of Laboratory Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People's Republic of China.
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24
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The emerging roles of exosome-derived noncoding RNAs in the tumor immune microenvironment and their future applications. Biomed Pharmacother 2022; 156:113863. [DOI: 10.1016/j.biopha.2022.113863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/03/2022] [Accepted: 10/09/2022] [Indexed: 11/24/2022] Open
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25
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Tenchov R, Sasso JM, Wang X, Liaw WS, Chen CA, Zhou QA. Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics. ACS NANO 2022; 16:17802-17846. [PMID: 36354238 PMCID: PMC9706680 DOI: 10.1021/acsnano.2c08774] [Citation(s) in RCA: 262] [Impact Index Per Article: 87.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/21/2022] [Indexed: 05/03/2023]
Abstract
Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties─innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity─allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.
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Affiliation(s)
- Rumiana Tenchov
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Janet M. Sasso
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Xinmei Wang
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Wen-Shing Liaw
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Chun-An Chen
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Qiongqiong Angela Zhou
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
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26
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Jiang Q, Tan XP, Zhang CH, Li ZY, Li D, Xu Y, Liu YX, Wang L, Ma Z. Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications. Cancers (Basel) 2022; 14:cancers14225693. [PMID: 36428785 PMCID: PMC9688215 DOI: 10.3390/cancers14225693] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.
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Affiliation(s)
- Qian Jiang
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China
- Department of Cardiovascular Medicine, Honghu Hospital of Traditional Chinese Medicine, Honghu 433200, China
| | - Xiao-Ping Tan
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- Digestive Disease Research Institution of Yangtze University, Yangtze University, Jingzhou 434023, China
| | - Cai-Hua Zhang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Zhi-Yuan Li
- Department of Cardiovascular Medicine, Honghu Hospital of Traditional Chinese Medicine, Honghu 433200, China
| | - Du Li
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Yan Xu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
| | - Yu Xuan Liu
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Lingzhi Wang
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
- NUS Centre for Cancer Research (N2CR), National University of Singapore, Singapore 117599, Singapore
- Correspondence: (Z.M.); (L.W.)
| | - Zhaowu Ma
- Department of Gastroenterology, First Affiliated Hospital of Yangtze University, Health Science Center, Yangtze University, Jingzhou 434023, China
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, China
- Correspondence: (Z.M.); (L.W.)
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27
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Ebrahimi N, Faghihkhorasani F, Fakhr SS, Moghaddam PR, Yazdani E, Kheradmand Z, Rezaei-Tazangi F, Adelian S, Mobarak H, Hamblin MR, Aref AR. Tumor-derived exosomal non-coding RNAs as diagnostic biomarkers in cancer. Cell Mol Life Sci 2022; 79:572. [PMID: 36308630 PMCID: PMC11802992 DOI: 10.1007/s00018-022-04552-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 09/02/2022] [Accepted: 09/04/2022] [Indexed: 12/24/2022]
Abstract
Almost all clinical oncologists agree that the discovery of reliable, accessible, and non-invasive biomarkers is necessary to decrease cancer mortality. It is possible to employ reliable biomarkers to diagnose cancer in the early stages, predict the patient prognosis, follow up the response to treatment, and estimate the risk of disease recurrence with high sensitivity and specificity. Extracellular vesicles (EVs), especially exosomes, have been the focus of translational research to develop such biomarkers over the past decade. The abundance and distribution of exosomes in bodily fluids, including serum, saliva, and urine, as well as their ability to transport various biomolecules (nucleic acids, proteins, and lipids) derived from their parent cells, make exosomes reliable, accessible, and potent biomarkers for diagnosis and follow-up of solid and hematopoietic tumors. In addition, exosomes play a vital role in various cellular processes, including tumor progression, by participating in intercellular communication. Although these advantages underline the high potential of tumor-derived exosomes as diagnostic biomarkers, the lack of standardized effective methods for their isolation, identification, and precise characterization makes their application challenging in clinical settings. We discuss the importance of non-coding RNAs (ncRNAs) in cellular processes, and the role of tumor-derived exosomes containing ncRNAs as potential biomarkers in several types of cancer. In addition, the advantages and challenges of these studies for translation into clinical applications are covered.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | | | - Siavash Seifollahy Fakhr
- Division of Biotechnology, Faculty of Applied Ecology, Agricultural Sciences and Biotechnology, Campus, Hamar, Norway
| | - Parichehr Roozbahani Moghaddam
- Department of Molecular Genetics, Faculty of Science, Tonekabon Branch, Islamic Azad University, Tehran, Mazandaran, Iran
| | - Elnaz Yazdani
- Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran
- Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Zahra Kheradmand
- Department of Agriculture, Islamic Azad University Maragheh Branch, Maragheh, Iran
| | - Fatemeh Rezaei-Tazangi
- Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Samaneh Adelian
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Halimeh Mobarak
- Clinical Pathologist, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.
| | - Amir Reza Aref
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
- Translational Medicine Group, Xsphera Biosciences, 6 Tide Street, Boston, MA, 02210, USA.
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28
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Sun P, Antwi SO, Sartorius K, Zheng X, Li X. Tumor Microenvironment, Clinical Features, and Advances in Therapy for Bone Metastasis in Gastric Cancer. Cancers (Basel) 2022; 14:4888. [PMID: 36230816 PMCID: PMC9563035 DOI: 10.3390/cancers14194888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 09/30/2022] [Accepted: 10/01/2022] [Indexed: 11/16/2022] Open
Abstract
Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9-13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer.
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Affiliation(s)
- Pengcheng Sun
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
| | - Samuel O. Antwi
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
| | - Kurt Sartorius
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
- School of Laboratory Medicine and Molecular Sciences, College of Health Sciences, University of Kwazulu-Natal, Durban 4041, South Africa
- UKZN Gastrointestinal Cancer Research Unit, University of Kwazulu-Natal, Durban 4041, South Africa
| | - Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
| | - Xiaodong Li
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
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29
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Zeng X, Xiao J, Bai X, Liu Y, Zhang M, Liu J, Lin Z, Zhang Z. Research progress on the circRNA/lncRNA-miRNA-mRNA axis in gastric cancer. Pathol Res Pract 2022; 238:154030. [PMID: 36116329 DOI: 10.1016/j.prp.2022.154030] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 07/14/2022] [Accepted: 07/16/2022] [Indexed: 01/19/2023]
Abstract
Gastric cancer is one of the most common malignant tumours worldwide. Genetic and epigenetic alterations are key factors in gastric carcinogenesis and drug resistance to chemotherapy. Competing endogenous RNA (ceRNA) regulation models have defined circRNA/lncRNA as miRNA sponges that indirectly regulate miRNA downstream target genes. The ceRNA regulatory network is related to the malignant biological behaviour of gastric cancer. The circRNA/lncRNA-miRNA-mRNA axis may be a marker for the early diagnosis and prognosis of gastric cancer and a potential therapeutic target for gastric cancer. Exosomal ncRNAs play an important role in gastric cancer and are expected to be ideal biomarkers for the diagnosis, prognosis, and treatment of gastric cancer. This review summarizes the specific ceRNA regulatory network (circRNA/lncRNA-miRNA-mRNA) discovered in gastric cancer in recent years, which may provide new ideas or strategies for early clinical diagnosis, further development, and application.
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Affiliation(s)
- Xuemei Zeng
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China
| | - Juan Xiao
- Department of Otorhinolaryngology, The Second Affiliated Hospital, Hengyang Medical School,University of South China, Hengyang 421001, China
| | - Xue Bai
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China
| | - Yiwen Liu
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China
| | - Meilan Zhang
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China
| | - Jiangrong Liu
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China
| | - Zixuan Lin
- Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Zhiwei Zhang
- Cancer Research Institute of Hengyang Medical School, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, China.
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HajiEsmailPoor Z, Tabnak P, Ahmadzadeh B, Ebrahimi SS, Faal B, Mashatan N. Role of hedgehog signaling related non-coding RNAs in developmental and pathological conditions. Biomed Pharmacother 2022; 153:113507. [DOI: 10.1016/j.biopha.2022.113507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/23/2022] [Accepted: 07/30/2022] [Indexed: 11/02/2022] Open
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Yi X, Chen J, Huang D, Feng S, Yang T, Li Z, Wang X, Zhao M, Wu J, Zhong T. Current perspectives on clinical use of exosomes as novel biomarkers for cancer diagnosis. Front Oncol 2022; 12:966981. [PMID: 36119470 PMCID: PMC9472136 DOI: 10.3389/fonc.2022.966981] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 08/01/2022] [Indexed: 12/11/2022] Open
Abstract
Exosomes are a heterogeneous subset of extracellular vesicles (EVs) that biogenesis from endosomes. Besides, exosomes contain a variety of molecular cargoes including proteins, lipids and nucleic acids, which play a key role in the mechanism of exosome formation. Meanwhile, exosomes are involved with physiological and pathological conditions. The molecular profile of exosomes reflects the type and pathophysiological status of the originating cells so could potentially be exploited for diagnostic of cancer. This review aims to describe important molecular cargoes involved in exosome biogenesis. In addition, we highlight exogenous factors, especially autophagy, hypoxia and pharmacology, that regulate the release of exosomes and their corresponding cargoes. Particularly, we also emphasize exosome molecular cargoes as potential biomarkers in liquid biopsy for diagnosis of cancer.
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Affiliation(s)
- Xiaomei Yi
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jie Chen
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Defa Huang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Shuo Feng
- English Teaching and Research Section, Gannan Healthcare Vocational College, Ganzhou, China
| | - Tong Yang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhengzhe Li
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoxing Wang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Minghong Zhao
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jiyang Wu
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Tianyu Zhong
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- *Correspondence: Tianyu Zhong,
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Cao D, Ou X, Li W, Ur-Rehman U. lncRNA PVT1 Targeting miR-423-5p Regulates Biological Behavior of Gastric Carcinoma Cells. INT J PHARMACOL 2022. [DOI: 10.3923/ijp.2022.1613.1622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Mishra LC, Pandey U, Gupta A, Gupta J, Sharma M, Mishra G. Alternating exosomes and their mimetics as an emergent strategy for targeted cancer therapy. Front Mol Biosci 2022; 9:939050. [PMID: 36032679 PMCID: PMC9399404 DOI: 10.3389/fmolb.2022.939050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 07/15/2022] [Indexed: 11/18/2022] Open
Abstract
Exosomes, a subtype of the class of extracellular vesicles and nano-sized particles, have a specific membrane structure that makes them an alternative proposition to combat with cancer through slight modification. As constituents of all most all the primary body fluids, exosomes establish the status of intercellular communication. Exosomes have specific proteins/mRNAs and miRNAs which serve as biomarkers, imparting a prognostic tool in clinical and disease pathologies. They have efficient intrinsic targeting potential and efficacy. Engineered exosomes are employed to deliver therapeutic cargos to the targeted tumor cell or the recipient. Exosomes from cancer cells bring about changes in fibroblast via TGFβ/Smad pathway, augmenting the tumor growth. These extracellular vesicles are multidimensional in terms of the functions that they perform. We herein discuss the uptake and biogenesis of exosomes, their role in various facets of cancer studies, cell-to-cell communication and modification for therapeutic and diagnostic use.
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Affiliation(s)
| | - Utkarsh Pandey
- Department of Zoology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Abhikarsh Gupta
- Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Jyotsna Gupta
- Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Monal Sharma
- Betterhumans Inc., Gainesville, FL, United States
| | - Gauri Mishra
- Department of Zoology, Swami Shraddhanand College, University of Delhi, New Delhi, India
- Division Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India
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Malik J, Klammer M, Rolny V, Chan HLY, Piratvisuth T, Tanwandee T, Thongsawat S, Sukeepaisarnjaroen W, Esteban JI, Bes M, Köhler B, Swiatek-de Lange M. Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma. World J Gastroenterol 2022; 28:3917-3933. [PMID: 36157551 PMCID: PMC9367234 DOI: 10.3748/wjg.v28.i29.3917] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 05/20/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein (AFP), protein induced by vitamin K absence/antagonist-II (PIVKA-II) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs (miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC.
AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers.
METHODS Our prospective, multicenter, case-control study recruited 660 participants (354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR (n = 60) and next-generation sequencing (n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs (including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-II via real-time quantitative PCR in training (n = 200) and validation cohorts (n = 300).
RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from (early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p (miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423 could significantly distinguish (Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-II was selected as the best combination, resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-II performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level (cycle threshold between 31.24 and 34.97).
CONCLUSION miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-II do not improve the diagnostic performance of the protein biomarkers.
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Affiliation(s)
| | | | | | - Henry Lik-Yuen Chan
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Hat Yai 90112, Thailand
| | - Tawesak Tanwandee
- Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Satawat Thongsawat
- Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | | | - Marta Bes
- Transfusion Safety Laboratory, Banc de Sang i Teixits, Barcelona 08005, Spain
| | - Bruno Köhler
- Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg 69120, Germany
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg 69120, Germany
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The Exosome Journey: From Biogenesis to Regulation and Function in Cancers. JOURNAL OF ONCOLOGY 2022; 2022:9356807. [PMID: 35898929 PMCID: PMC9313905 DOI: 10.1155/2022/9356807] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/01/2022] [Accepted: 06/20/2022] [Indexed: 12/26/2022]
Abstract
Exosomes are a type of small endosomal-derived vesicles ranging from 30 to 150 nm, which can serve as functional mediators in cell-to-cell communication and various physiological and pathological processes. In recent years, exosomes have emerged as crucial mediators of intracellular communication among tumor cells, immune cells, and stromal cells, which can shuttle bioactive molecules, such as proteins, lipids, RNA, and DNA. Exosomes exhibit the high bioavailability, biological stability, targeting specificity, low toxicity, and immune characteristics, suggesting their potentials in the diagnosis and treatment of cancers. They can be applied as an effective tool in the diagnostics, therapeutics, and drug delivery in cancers. This review summarizes the regulation and functions of exosomes in various cancers to augment our understanding of exosomes, which paves the way for parallel advancements in the therapeutic approach of cancers. In this review, we also discuss the challenges and prospects for clinical application of exosome-based diagnostics and therapeutics for cancers.
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Shi Y, Qiu B, Huang L, Lin J, Li Y, Ze Y, Huang C, Yao Y. Exosomes and ferroptosis: roles in tumour regulation and new cancer therapies. PeerJ 2022; 10:e13238. [PMID: 35497192 PMCID: PMC9053300 DOI: 10.7717/peerj.13238] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/18/2022] [Indexed: 02/05/2023] Open
Abstract
Research on the biological role of exosomes is rapidly developing, and recent evidence suggests that exosomal effects involve ferroptosis. Exosomes derived from different tissues inhibit ferroptosis, which increases tumour cell chemoresistance. Therefore, exosome-mediated regulation of ferroptosis may be leveraged to design anticancer drugs. This review discusses three pathways of exosome-mediated inhibition of ferroptosis: (1) the Fenton reaction; (2) the ferroptosis defence system, including the Xc-GSH-GPX4 axis and the FSP1/CoQ10/NAD(P)H axis; and (3) lipid peroxidation. We also summarize three recent approaches for combining exosomes and ferroptosis in oncology therapy: (1) promoting exosome-inhibited ferroptosis to enhance chemotherapy; (2) encapsulating exosomes with ferroptosis inducers to inhibit cancers; and (3) developing therapies that combine exosomal inhibitors and ferroptosis inducers. This review will contribute toward establishing effective cancer therapies.
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Affiliation(s)
- Yixin Shi
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bingrun Qiu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Linyang Huang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jie Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yiling Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yiting Ze
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chenglong Huang
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, China
| | - Yang Yao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Liu K, Gao X, Kang B, Liu Y, Wang D, Wang Y. The Role of Tumor Stem Cell Exosomes in Cancer Invasion and Metastasis. Front Oncol 2022; 12:836548. [PMID: 35350566 PMCID: PMC8958025 DOI: 10.3389/fonc.2022.836548] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/07/2022] [Indexed: 12/12/2022] Open
Abstract
Exosomes are lipid membrane bilayer-encapsulated vesicles secreted by cells into the extracellular space. They carry abundant inclusions (such as nucleic acids, proteins, and lipids) that play pivotal roles in intercellular communication. Tumor stem cells are capable of self-renewal and are crucial for survival, proliferation, drug resistance, metastasis, and recurrence of tumors. The miRNAs (microRNAs) in exosomes have various functions, such as participating in inflammatory response, cell migration, proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition. Tumor stem cells secrete exosomes that act as important messengers involved in various tumor processes and several studies provide increasing evidence supporting the importance of these exosomes in tumor recurrence and metastasis. This review primarily focuses on the production and secretion of exosomes from tumors and tumor stem cells and their effects on cancer progression. Cancer stem cancer derived exosome play an important massager in the tumor microenvironment. It also emphasizes on the study of tumor stem cell exosomes in the light of cancer metastasis and recurrence aiming to provide valuable insights and novel perspectives, which could be beneficial for developing effective diagnostic and treatment strategies.
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Affiliation(s)
- Kun Liu
- Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, ChangChun, China
| | - Xin Gao
- Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, ChangChun, China
| | - Baoqiang Kang
- Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, ChangChun, China
| | - Yunpeng Liu
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Dingding Wang
- School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yi Wang
- Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, ChangChun, China
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Volovat SR, Ursulescu CL, Moisii LG, Volovat C, Boboc D, Scripcariu D, Amurariti F, Stefanescu C, Stolniceanu CR, Agop M, Lungulescu C, Volovat CC. The Landscape of Nanovectors for Modulation in Cancer Immunotherapy. Pharmaceutics 2022; 14:397. [PMID: 35214129 PMCID: PMC8875018 DOI: 10.3390/pharmaceutics14020397] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/01/2022] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy's efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed.
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Affiliation(s)
- Simona-Ruxandra Volovat
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (S.-R.V.); (D.B.); (F.A.)
| | - Corina Lupascu Ursulescu
- Department of Radiology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (C.L.U.); (L.G.M.); (C.C.V.)
| | - Liliana Gheorghe Moisii
- Department of Radiology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (C.L.U.); (L.G.M.); (C.C.V.)
| | - Constantin Volovat
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (S.-R.V.); (D.B.); (F.A.)
- Department of Medical Oncology, “Euroclinic” Center of Oncology, 2 Vasile Conta Str., 700106 Iaşi, Romania
| | - Diana Boboc
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (S.-R.V.); (D.B.); (F.A.)
| | - Dragos Scripcariu
- Department of Surgery, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania;
| | - Florin Amurariti
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (S.-R.V.); (D.B.); (F.A.)
| | - Cipriana Stefanescu
- Department of Biophysics and Medical Physics-Nuclear Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (C.S.); (C.R.S.)
| | - Cati Raluca Stolniceanu
- Department of Biophysics and Medical Physics-Nuclear Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (C.S.); (C.R.S.)
| | - Maricel Agop
- Physics Department, “Gheorghe Asachi” Technical University, Prof. Dr. Docent Dimitrie Mangeron Rd., No. 59A, 700050 Iaşi, Romania;
| | - Cristian Lungulescu
- Department of Medical Oncology, University of Medicine and Pharmacy, 200349 Craiova, Romania;
| | - Cristian Constantin Volovat
- Department of Radiology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iaşi, Romania; (C.L.U.); (L.G.M.); (C.C.V.)
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Cappello F, Fais S. Extracellular vesicles in cancer pros and cons: the importance of the evidence-based medicine. Semin Cancer Biol 2022; 86:4-12. [DOI: 10.1016/j.semcancer.2022.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 01/18/2022] [Accepted: 01/28/2022] [Indexed: 12/17/2022]
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Li J, Sun L, Chen Y, Zhu J, Shen J, Wang J, Gu Y, Zhang G, Wang M, Shi T, Chen W. Gastric cancer-derived exosomal miR-135b-5p impairs the function of Vγ9Vδ2 T cells by targeting specificity protein 1. Cancer Immunol Immunother 2022; 71:311-325. [PMID: 34159436 DOI: 10.1007/s00262-021-02991-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 06/16/2021] [Indexed: 12/24/2022]
Abstract
Recent studies have shown that tumor-derived exosomes participate in the communication between tumor cells and their microenvironment and mediate malignant biological behaviors including immune escape. In this study, we found that gastric cancer (GC) cell-derived exosomes could be effectively uptaken by Vγ9Vδ2 T cells, decrease the cell viability of Vγ9Vδ2 T cells, induce apoptosis, and reduce the production of cytotoxic cytokines IFN-γ and TNF-α. Furthermore, we demonstrated that exosomal miR-135b-5p was delivered into Vγ9Vδ2 T cells. Exosomal miR-135b-5p impaired the function of Vγ9Vδ2 T cells by targeting specificity protein 1 (SP1). More importantly, blocking the SP1 function by Plicamycin, an SP1 inhibitor, abolished the effect of stable miR-135b-5p knockdown GC cell-derived exosomes on Vγ9Vδ2 T cell function. Collectively, our results suggest that GC cell-derived exosomes impair the function of Vγ9Vδ2 T cells via miR-135b-5p/SP1 pathway, and targeting exosomal miR-135b-5p/SP1 axis may improve the efficiency of GC immunotherapy based on Vγ9Vδ2 T cells.
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Affiliation(s)
- Juntao Li
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China
| | - Linqing Sun
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China
| | - Yanjun Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China
| | - Jinghan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China
| | - Jin Shen
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
| | - Jiayu Wang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China
| | - Yanzheng Gu
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
| | - Guangbo Zhang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China
| | - Mingyuan Wang
- Suzhou Red Cross Blood Center, 355 Shizi Road, Suzhou, China
| | - Tongguo Shi
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China.
- Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China.
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China.
- Jiangsu Province, 708 Renmin Road, Suzhou, 215100, China.
| | - Weichang Chen
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China.
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China.
- Jiangsu Province, 50 Donghuan Road, Suzhou, 215100, China.
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Tang D, Liu S, Shen H, Deng G, Zeng S. Extracellular Vesicles Promote the Formation of Pre-Metastasis Niche in Gastric Cancer. Front Immunol 2022; 13:813015. [PMID: 35173726 PMCID: PMC8841609 DOI: 10.3389/fimmu.2022.813015] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Globally, gastric cancer (GC) ranks fourth in the incidence of malignant tumors. The early clinical manifestations of GC lack specificity. Most patients are already at an advanced stage when they are first diagnosed, and their late progression is mainly due to peritoneal metastasis. A pre-metastatic microenvironment is formed, before the macroscopic tumor metastasis. Extracellular vesicles (EVs) are nanovesicles released by cells into body fluids. Recent studies have shown that EVs can affect the tumor microenvironment by carrying cargos to participate in cell-to-cell communication. EVs derived from GC cells mediate the regulation of the pre-metastasis niche and act as a coordinator between tumor cells and normal stroma, immune cells, inflammatory cells, and tumor fibroblasts to promote tumor growth and metastasis. This review highlights the regulatory role of EVs in the pre-metastatic niche of GC and mulls EVs as a potential biomarker for liquid biopsy.
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Affiliation(s)
- Diya Tang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Shanshan Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hong Shen
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Gongping Deng
- Department of Emergency, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
- *Correspondence: Gongping Deng, ; Shan Zeng,
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Gongping Deng, ; Shan Zeng,
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42
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Jahan S, Mukherjee S, Ali S, Bhardwaj U, Choudhary RK, Balakrishnan S, Naseem A, Mir SA, Banawas S, Alaidarous M, Alyenbaawi H, Iqbal D, Siddiqui AJ. Pioneer Role of Extracellular Vesicles as Modulators of Cancer Initiation in Progression, Drug Therapy, and Vaccine Prospects. Cells 2022; 11:490. [PMID: 35159299 PMCID: PMC8833976 DOI: 10.3390/cells11030490] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/25/2022] [Accepted: 01/28/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer is one of the leading diseases, causing deaths worldwide. Nearly 10 million deaths were reported in 2020 due to cancer alone. Several factors are involved in cancer progressions, such as lifestyle and genetic characteristics. According to a recent report, extracellular vesicles (EVs) are involved in cancer initiation, progression, and therapy failure. EVs can play a major role in intracellular communication, the maintenance of tissue homeostasis, and pathogenesis in several types of diseases. In a healthy person, EVs carry different cargoes, such as miRNA, lncRNA etc., to help other body functions. On the other hand, the same EV in a tumor microenvironment carries cargoes such as miRNA, lncRNA, etc., to initiate or help cancer progression at various stages. These stages may include the proliferation of cells and escape from apoptosis, angiogenesis, cell invasion, and metastasis, reprogramming energy metabolism, evasion of the immune response, and transfer of mutations. Tumor-derived EVs manipulate by altering normal functions of the body and affect the epigenetics of normal cells by limiting the genetic makeup through transferring mutations, histone modifications, etc. Tumor-derived EVs also pose therapy resistance through transferring drug efflux pumps and posing multiple drug resistances. Such EVs can also help as biomarkers for different cancer types and stages, which ultimately help with cancer diagnosis at early stages. In this review, we will shed light on EVs' role in performing normal functions of the body and their position in different hallmarks of cancer, in altering the genetics of a normal cell in a tumor microenvironment, and their role in therapy resistance, as well as the importance of EVs as diagnostic tools.
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Affiliation(s)
- Sadaf Jahan
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Shouvik Mukherjee
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Shaheen Ali
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Urvashi Bhardwaj
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Ranjay Kumar Choudhary
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Santhanaraj Balakrishnan
- Medical Equipment Technology, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Asma Naseem
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Shabir Ahmad Mir
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Saeed Banawas
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
- Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA
| | - Mohammed Alaidarous
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Hadeel Alyenbaawi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Danish Iqbal
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Arif Jamal Siddiqui
- Department of Biology, College of Science, University of Hail, Hail 81451, Saudi Arabia
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Zeng L, Liao Q, Zeng X, Ye J, Yang X, Zhu S, Tang H, Liu G, Cui W, Ma S, Cui S. Noncoding RNAs and hyperthermic intraperitoneal chemotherapy in advanced gastric cancer. Bioengineered 2022; 13:2623-2638. [PMID: 35089117 PMCID: PMC8973587 DOI: 10.1080/21655979.2021.2021348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors globally. About 20-30% of patients with gastric cancer show peritoneal implantation metastasis at the first diagnosis. Peritoneal metastasis is responsible for 70% of deaths of patients with advanced gastric cancer. Although there are many ways to treat advanced gastric cancer, the prognosis of patients with recurrence is unsatisfactory. An auxiliary treatment with hyperthermic intraperitoneal chemotherapy (HIPEC), is an internationally recognized recommended treatment for advanced gastric cancer. A series of clinical trials have shown that HIPEC significantly improves the overall survival of patients with cancer. Compared with the cytoreductive surgery (CRS) alone, HIPEC combined with CRS markedly reduced the rate of peritoneal metastasis in patients with ovarian cancer and colorectal cancer. It has been demonstrated that HIPEC alters transcription of many genes by affecting non-coding RNAs, which may contribute to the suppressive effect of HIPEC on the synthesis of nucleic acids and proteins in cancer cells. This paper reviews the recent advances in understanding the role of non-coding RNAs in tumor invasion and metastasis of advanced gastric cancer. We also consider changes in noncoding RNA levels and other molecules in advanced gastric cancer cases treated with HIPEC. We hope that our review will provide a reference for future research on molecular epidemiology and etiology of advanced gastric cancer and promote precise treatment of this malignancy using HIPEC.
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Affiliation(s)
- Lisi Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Quanxing Liao
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jiacai Ye
- Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xianzi Yang
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Siyu Zhu
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Gaojie Liu
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Weiwen Cui
- Department of Bioengineering, University of California, Berkeley, California, USA
| | - Shaohua Ma
- Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.,Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China
| | - Shuzhong Cui
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.,State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
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Cheng H, Yang Q, Wang R, Luo R, Zhu S, Li M, Li W, Chen C, Zou Y, Huang Z, Xie T, Wang S, Zhang H, Tian Q. Emerging Advances of Detection Strategies for Tumor-Derived Exosomes. Int J Mol Sci 2022; 23:868. [PMID: 35055057 PMCID: PMC8775838 DOI: 10.3390/ijms23020868] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022] Open
Abstract
Exosomes derived from tumor cells contain various molecular components, such as proteins, RNA, DNA, lipids, and carbohydrates. These components play a crucial role in all stages of tumorigenesis and development. Moreover, they reflect the physiological and pathological status of parental tumor cells. Recently, tumor-derived exosomes have become popular biomarkers for non-invasive liquid biopsy and the diagnosis of numerous cancers. The interdisciplinary significance of exosomes research has also attracted growing enthusiasm. However, the intrinsic nature of tumor-derived exosomes requires advanced methods to detect and evaluate the complex biofluid. This review analyzes the relationship between exosomes and tumors. It also summarizes the exosomal biological origin, composition, and application of molecular markers in clinical cancer diagnosis. Remarkably, this paper constitutes a comprehensive summary of the innovative research on numerous detection strategies for tumor-derived exosomes with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.
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Affiliation(s)
- Huijuan Cheng
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Qian Yang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Rongrong Wang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Ruhua Luo
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Shanshan Zhu
- Public Health Institutes, Hangzhou Normal University, Hangzhou 311121, China;
| | - Minhui Li
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Wenqi Li
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Cheng Chen
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Yuqing Zou
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Zhihua Huang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Tian Xie
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Shuling Wang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Honghua Zhang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Qingchang Tian
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
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Ferri C, Di Biase A, Bocchetti M, Zappavigna S, Wagner S, Le Vu P, Luce A, Cossu AM, Vadakekolathu J, Miles A, Boocock DJ, Robinson A, Schwerdtfeger M, Tirino V, Papaccio F, Caraglia M, Regad T, Desiderio V. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res 2022; 41:20. [PMID: 35016717 PMCID: PMC8751098 DOI: 10.1186/s13046-021-02233-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 12/22/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs). METHODS Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa. RESULTS Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model. CONCLUSIONS We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.
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Affiliation(s)
- Carmela Ferri
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy
- Medicina Futura Group, Coleman S.p.A, Via Alcide De Gasperi 107/109/111, 80011, Acerra, NA, Italy
| | - Anna Di Biase
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - Marco Bocchetti
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
- Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031, Ariano Irpino, Italy
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy
| | - Sarah Wagner
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - Pauline Le Vu
- Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Coxford Rd, Southampton, SO16 5YA, UK
| | - Amalia Luce
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - Alessia Maria Cossu
- Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031, Ariano Irpino, Italy
| | - Jayakumar Vadakekolathu
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - Amanda Miles
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - David J Boocock
- The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK
| | - Alex Robinson
- Department of Life Sciences, Faculty of Health, Education and Life Sciences, Birmingham City University, Birmingham, B15 3TN, UK
| | - Melanie Schwerdtfeger
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| | - Virginia Tirino
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| | - Federica Papaccio
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Via S. Allende, 84081, Baronissi, Italy
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
- Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031, Ariano Irpino, Italy.
| | - Tarik Regad
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy
| | - Vincenzo Desiderio
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
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LIU L, HU D. SUFU reduced pancreatic cancer cell growth by Wnt/β-catenin signaling pathway. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.61721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Limin LIU
- The Second Affiliated Hospital of Soochow University, China; Yancheng First People’s Hospital, China; The Fourth Affiliated Hospital of Nantong University, China
| | - Duanmin HU
- The Second Affiliated Hospital of Soochow University, China
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Bao CH, Guo L. Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway. Anticancer Agents Med Chem 2022; 22:864-873. [PMID: 34238170 DOI: 10.2174/1871520621666210707095833] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/19/2021] [Accepted: 05/04/2021] [Indexed: 11/22/2022]
Abstract
The article entitled “miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway”, by Chen-Hui Bao and Lin Guo, has been retracted on the request of the Author in light of the changes to the University’s promotion policy, due to which the article needs further content. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. Kindly see Bentham Science Policy on Article retraction at the link https://benthamscience.com/journals/anti-canceragents-in-medicinal-chemistry/editorial-policies/ Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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Affiliation(s)
- Chen-Hui Bao
- Department of General surgery, ShengJing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang City 110004, Liaoning Province, China
| | - Lin Guo
- Department of General surgery, ShengJing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang City 110004, Liaoning Province, China
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Xue P, Huang S, Han X, Zhang C, Yang L, Xiao W, Fu J, Li H, Zhou Y. Exosomal miR-101-3p and miR-423-5p inhibit medulloblastoma tumorigenesis through targeting FOXP4 and EZH2. Cell Death Differ 2022; 29:82-95. [PMID: 34294888 PMCID: PMC8738741 DOI: 10.1038/s41418-021-00838-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 07/08/2021] [Accepted: 07/12/2021] [Indexed: 01/03/2023] Open
Abstract
Exosomal microRNAs (miRNAs) have been implicated in the development and progression of a variety of tumors; however, whether they contribute to medulloblastoma (MB) tumorigenesis remains to be elucidated. To address this, we first characterized the miRNA profiles of circulating exosomes by miRNA sequencing to identify miRNAs differentially expressed between children with MB and healthy controls. Then, we conducted in vitro and in vivo functional assays with the identified miRNAs and their predicted targets. We found that, compared with healthy controls, 35 miRNAs were upregulated and 5 downregulated in exosomes isolated from the plasma of MB patients. We further found that the expression of miR-101-3p and miR-423-5p was significantly higher in plasma exosomes from MB patients than in healthy controls in an expanded cohort and these exosomal miRNAs could be delivered to tumor cells via exosomes. An in vitro functional analysis of miR-101-3p and miR-423-5p showed that treating MB cells with the corresponding mimics significantly inhibited the proliferation, colony-forming ability, migratory ability, and invasive capacity of tumor cells, and promoted cell apoptosis. Additionally, miR-101-3p and miR-423-5p were found to act as tumor suppressors by directly targeting a common gene, FOXP4, which encodes a transcription factor with a vital role in embryonic development and tumorigenesis. Moreover, miR-101-3p also targeted EZH2, a histone methyltransferase, to reinforce its tumor inhibitory effects. Using a xenograft nude mouse model of MB, we further identified that the overexpression of miR-101-3p and miR-423-5p inhibited tumorigenesis in vivo. Our findings provide novel insights into the functions of exosomal miRNAs in mediating MB progression and suggest a potential therapeutic approach for the treatment of children with MB.
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Affiliation(s)
- Ping Xue
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
- Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China
| | - Saihua Huang
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases (Fudan University), Shanghai, 201102, China
| | - Xiao Han
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases (Fudan University), Shanghai, 201102, China
| | - Caiyan Zhang
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Lan Yang
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Wenfeng Xiao
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Jinrong Fu
- General Department, Children's Hospital of Fudan University, Shanghai, China
| | - Hao Li
- Department of Neurosurgery, Children's Hospital of Fudan University, Shanghai, China.
| | - Yufeng Zhou
- Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
- National Health Commission (NHC) Key Laboratory of Neonatal Diseases (Fudan University), Shanghai, 201102, China.
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Morales-Pison S, Jara L, Carrasco V, Gutiérrez-Vera C, Reyes JM, Gonzalez-Hormazabal P, Carreño LJ, Tapia JC, Contreras HR. Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells. Int J Mol Sci 2021; 23:ijms23010380. [PMID: 35008806 PMCID: PMC8745459 DOI: 10.3390/ijms23010380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.
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Affiliation(s)
- Sebastian Morales-Pison
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Lilian Jara
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Valentina Carrasco
- Laboratorio de Biología Estructural y Molecular, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago 8380453, Chile;
| | - Cristian Gutiérrez-Vera
- Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (C.G.-V.); (L.J.C.)
| | | | - Patricio Gonzalez-Hormazabal
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Leandro J. Carreño
- Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (C.G.-V.); (L.J.C.)
| | - Julio C. Tapia
- Laboratorio de Transformación Celular, Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
- Correspondence: (J.C.T.); (H.R.C.); Tel.: +56-2-9788647 (J.C.T.)
| | - Héctor R. Contreras
- Laboratorio de Biología Celular y Molecular, Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
- Correspondence: (J.C.T.); (H.R.C.); Tel.: +56-2-9788647 (J.C.T.)
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50
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Yan Z, Sheng Z, Zheng Y, Feng R, Xiao Q, Shi L, Li H, Yin C, Luo H, Hao C, Wang W, Zhang B. Cancer-associated fibroblast-derived exosomal miR-18b promotes breast cancer invasion and metastasis by regulating TCEAL7. Cell Death Dis 2021; 12:1120. [PMID: 34853307 PMCID: PMC8636636 DOI: 10.1038/s41419-021-04409-w] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/06/2021] [Accepted: 11/15/2021] [Indexed: 11/09/2022]
Abstract
Studies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3'UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.
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Affiliation(s)
- Ziqian Yan
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Zhimei Sheng
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Yuanhang Zheng
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Ruijun Feng
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Qinpei Xiao
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Lihong Shi
- Department of Pharmacology, Weifang Medical University, Weifang, Shandong, China
| | - Hongli Li
- Department of Medicine Research Center, Weifang Medical University, Weifang, Shandong, China
| | - Chonggao Yin
- Department of Medicine Research Center, Weifang Medical University, Weifang, Shandong, China
| | - Hao Luo
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Chong Hao
- Department of Oncology, Maternal and Child Health Care Hospital of Zibo, Zibo, Shandong, China
| | - Wenhao Wang
- Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Baogang Zhang
- Department of Pathology, Weifang Medical University, Weifang, Shandong, China.
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
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