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1
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Nor WMFSBWM, Kwong SC, Fuzi AAM, Said NABM, Jamil AHA, Lee YY, Lee SC, Lim YAL, Chung I. Linking microRNA to metabolic reprogramming and gut microbiota in the pathogenesis of colorectal cancer (Review). Int J Mol Med 2025; 55:46. [PMID: 39820715 PMCID: PMC11759585 DOI: 10.3892/ijmm.2025.5487] [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: 06/11/2024] [Accepted: 12/03/2024] [Indexed: 01/19/2025] Open
Abstract
Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.
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Affiliation(s)
| | - Soke Chee Kwong
- Centre for Population Health (CePH), Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Afiqah Alyaa Md Fuzi
- Office of Deputy Vice Chancellor (Research and Innovation), Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Nur Akmarina Binti Mohd Said
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Amira Hajirah Abd Jamil
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Malaysia
| | - Soo Ching Lee
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Yvonne Ai-Lian Lim
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Ivy Chung
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
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2
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Matboli M, Hossam N, Farag D, Hassan M, Shehata H, Aboelhussein M, Ismail N, Eissa S. miRNAs: possible regulators of toll like receptors and inflammatory tumor microenvironment in colorectal cancer. BMC Cancer 2024; 24:824. [PMID: 38987740 PMCID: PMC11238347 DOI: 10.1186/s12885-024-12417-0] [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: 12/28/2023] [Accepted: 05/23/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways. AIM To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells. METHODS From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines. RESULTS Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis. CONCLUSION MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment.
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Affiliation(s)
- Marwa Matboli
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Nourhan Hossam
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Doaa Farag
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt
| | - Mohamed Hassan
- Department of Biology/Zoology, Biotechnology Program, Faculty of Science, Port Said University, Port Said, Egypt
- Zewail City for Science & Technology, Center for Genomics, Helmy Institute for Medical Science, Giza, Egypt
| | - Hanan Shehata
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Marwa Aboelhussein
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nahed Ismail
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, 60612, USA
| | - Sanaa Eissa
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
- MASRI Research Institute, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
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3
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Nagainallur Ravichandran S, Das D, Dayananda EK, Dey A, Banerjee A, Sun-Zhang A, Zhang H, Sun XF, Pathak S. A Review on Emerging Techniques for Diagnosis of Colorectal Cancer. Cancer Invest 2024; 42:119-140. [PMID: 38404236 DOI: 10.1080/07357907.2024.2315443] [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: 06/11/2023] [Accepted: 02/02/2024] [Indexed: 02/27/2024]
Abstract
Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.
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Affiliation(s)
- Shruthi Nagainallur Ravichandran
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Diptimayee Das
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Erica Katriel Dayananda
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Amit Dey
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Antara Banerjee
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Alexander Sun-Zhang
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Stockholm, Sweden
| | - Hong Zhang
- Faculty of Medicine and Health, School of Medical Sciences, Orebro University, Örebro, Sweden
| | - Xiao-Feng Sun
- Division of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Surajit Pathak
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
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4
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Wu S, Wu Y, Deng S, Lei X, Yang X. The Impact of miR-122 on Cancer. Curr Pharm Biotechnol 2024; 25:1489-1499. [PMID: 38258767 DOI: 10.2174/0113892010272106231109065912] [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: 07/13/2023] [Revised: 09/11/2023] [Accepted: 09/21/2023] [Indexed: 01/24/2024]
Abstract
MiRNAs are confirmed to be a kind of short and eminently conserved noncoding RNAs, which regulate gene expression at the post-transcriptional level via binding to the 3'- untranslated region (3'-UTR) of targeting multiple target messenger RNAs. Recently, growing evidence stresses the point that they play a crucial role in a variety of pathological processes, including human cancers. Dysregulated miRNAs act as oncogenes or tumor suppressor genes in many cancer types. Among them, we noticed that miR-122 has been widely reported to significantly influence carcinogenicity in a variety of tumors by regulating target genes and signaling pathways. Here, we focused on the expression of miR-122 in regulatory mechanisms and tumor biological processes. We also discussed the effects of miR-122 dysregulation in various types of human malignancies and the potential to develop new molecular miR-122-targeted therapies. The present review suggests that miR-122 may be a potentially useful cancer diagnosis and treatment biomarker. More clinical diagnoses need to be further launched in the future. A promising direction to improve the outcomes for cancer patients will likely combine miR-122 with other traditional tumor biomarkers.
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Affiliation(s)
- Shijie Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
| | - Yiwen Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
| | - Sijun Deng
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan, 421001, P.R. China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan, 421001, P.R. China
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5
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Mohammed OA. From strings to signals: Unraveling the impact of miRNAs on diagnosis, and progression of colorectal cancer. Pathol Res Pract 2023; 251:154857. [PMID: 37804545 DOI: 10.1016/j.prp.2023.154857] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 09/21/2023] [Accepted: 10/03/2023] [Indexed: 10/09/2023]
Abstract
Colorectal cancer (CRC) stands as the third most prevalent ailment globally and represents the primary cause of mortality associated with cancer. Significant advancements have been made in the clinical management of patients with CRC, encompassing the development of more streamlined methodologies and a diverse array of biomarkers utilized for prognostic, diagnostic, and predictive objectives. MicroRNAs (miRNAs, miRs) play a key role in the development of CRC by modulating the expression of their target genes, which govern a number of metabolic and cellular processes. They are related to malignant traits such as enhanced invasive and proliferative capacity, evasion of apoptosis, cell cycle aberration, and promotion of angiogenesis through dysregulation in their function. This review's objectives were to examine miRNA biogenesis, provide an updated list of oncogenic and tumor suppressor miRNAs, and discuss the likely causes of miRNA dysregulation in CRC. Additionally, we discuss the diagnostic and predictive functions of miRNAs in CRC and summarize their biological significance and clinical potential.
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Affiliation(s)
- Osama A Mohammed
- Department of Clinical Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
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6
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Al-Gazally ME, Khan R, Imran M, Ramírez-Coronel AA, Alshahrani SH, Altalbawy FMA, Turki Jalil A, Romero-Parra RM, Zabibah RS, Shahid Iqbal M, Karampoor S, Mirzaei R. The role and mechanism of action of microRNA-122 in cancer: Focusing on the liver. Int Immunopharmacol 2023; 123:110713. [PMID: 37523968 DOI: 10.1016/j.intimp.2023.110713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 07/08/2023] [Accepted: 07/24/2023] [Indexed: 08/02/2023]
Abstract
microRNA-122 (miR-122) is a highly conserved microRNA that is predominantly expressed in the liver and plays a critical role in the regulation of liver metabolism. Recent studies have shown that miR-122 is involved in the pathogenesis of various types of cancer, particularly liver cancer. In this sense, The current findings highlighted the potential role of miR-122 in regulating many vital processes in cancer pathophysiology, including apoptosis, signaling pathway, cell metabolism, immune system response, migration, and invasion. These results imply that miR-122, which has been extensively studied for its biological functions and potential therapeutic applications, acts as a tumor suppressor or oncogene in cancer development. We first provide an overview and summary of the physiological function and mode of action of miR-122 in liver cancer. We will examine the various signaling pathways and molecular mechanisms through which miR-122 exerts its effects on cancer cells, including the regulation of oncogenic and tumor suppressor genes, the modulation of cell proliferation and apoptosis, and the regulation of metastasis. Most importantly, we will also discuss the potential diagnostic and therapeutic applications of miR-122 in cancer, including the development of miRNA-based biomarkers for cancer diagnosis and prognosis, and the potential use of miR-122 as a therapeutic target for cancer treatment.
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Affiliation(s)
| | - Ramsha Khan
- MBBS, Nawaz Sharif Medical College, Gujrat, Pakistan
| | - Muhammad Imran
- MBBS, Multan Medical and Dental College, Multan, Pakistan
| | | | | | - Farag M A Altalbawy
- National Institute of Laser Enhanced Sciences (NILES), University of Cairo, Giza 12613, Egypt; Department of Chemistry, University College of Duba, University of Tabuk, Tabuk, Saudi Arabia
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla 51001, Iraq
| | | | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Muhammad Shahid Iqbal
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, 11942 Alkharj, Saudi Arabia
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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7
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Tariq L, Arafah A, Sehar N, Ali A, Khan A, Rasool I, Rashid SM, Ahmad SB, Beigh S, Dar TUH, Rehman MU. Novel insights on perils and promises of miRNA in understanding colon cancer metastasis and progression. Med Oncol 2023; 40:282. [PMID: 37639075 DOI: 10.1007/s12032-023-02099-2] [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: 05/23/2023] [Accepted: 06/19/2023] [Indexed: 08/29/2023]
Abstract
Colorectal cancer (CRC) is the third highest frequent malignancy and ultimate critical source of cancer-associated mortality around the world. Regardless of latest advances in molecular and surgical targeted medicines that have increased remedial effects in CRC patients, the 5-year mortality rate for CRC patients remains dismally low. Evidence suggests that microRNAs (miRNAs) execute an essential part in the development and spread of CRC. The miRNAs are a type of short non-coding RNA that exhibited to control the appearance of tumor suppressor genes and oncogenes. miRNA expression profiling is already being utilized in clinical practice as analytical and prognostic biomarkers to evaluate cancer patients' tumor genesis, advancement, and counteraction to drugs. By modulating their target genes, dysregulated miRNAs are linked to malignant characteristics (e.g., improved proliferative and invasive capabilities, cell cycle aberration, evasion of apoptosis, and promotion of angiogenesis). This review presents an updated summary of circulatory miRNAs, tumor-suppressive and oncogenic miRNAs, and the potential reasons for dysregulated miRNAs in CRC. Further we will explore the critical role of miRNAs in CRC drug resistance.
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Affiliation(s)
- Lubna Tariq
- Department of Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, Jammu and Kashmir, 183254, India
| | - Azher Arafah
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Nouroz Sehar
- Centre for Translational and Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Aarif Ali
- Division of Veterinary Biochemistry, Faculty of Veterinary Science and Animal Husbandry, SKUAST-Kashmir, Alusteng, Shuhama, Srinagar, Jammu and Kashmir, 190006, India
| | - Andleeb Khan
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142, Jazan, Saudi Arabia
| | - Iyman Rasool
- Department of Pathology, Government Medical College (GMC-Srinagar), Karanagar, Srinagar, Jammu and Kashmir, 190006, India
| | - Shahzada Mudasir Rashid
- Division of Veterinary Biochemistry, Faculty of Veterinary Science and Animal Husbandry, SKUAST-Kashmir, Alusteng, Shuhama, Srinagar, Jammu and Kashmir, 190006, India
| | - Sheikh Bilal Ahmad
- Division of Veterinary Biochemistry, Faculty of Veterinary Science and Animal Husbandry, SKUAST-Kashmir, Alusteng, Shuhama, Srinagar, Jammu and Kashmir, 190006, India
| | - Saba Beigh
- Department of Public Health, Faculty of Applied Medical Science, Al Baha University, 65431, Al Baha, Saudi Arabia
| | - Tanveer Ul Hassan Dar
- Department of Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, Jammu and Kashmir, 183254, India
| | - Muneeb U Rehman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.
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8
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Chakrabortty A, Patton DJ, Smith BF, Agarwal P. miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer. Genes (Basel) 2023; 14:1375. [PMID: 37510280 PMCID: PMC10378777 DOI: 10.3390/genes14071375] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/25/2023] [Accepted: 06/25/2023] [Indexed: 07/30/2023] Open
Abstract
MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target.
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Affiliation(s)
- Atonu Chakrabortty
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Daniel J Patton
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Bruce F Smith
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Payal Agarwal
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
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9
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Tristán AI, González-Flores E, Salmerón ADM, Abreu AC, Caba O, Jiménez-Luna C, Melguizo C, Prados J, Fernández I. Serum nuclear magnetic resonance metabolomics analysis of human metastatic colorectal cancer: Biomarkers and pathway analysis. NMR IN BIOMEDICINE 2023; 36:e4935. [PMID: 36945883 DOI: 10.1002/nbm.4935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 03/08/2023] [Accepted: 03/09/2023] [Indexed: 06/18/2023]
Abstract
We describe the use of nuclear magnetic resonance metabolomics to analyze blood serum samples from healthy individuals (n = 26) and those with metastatic colorectal cancer (CRC; n = 57). The assessment, employing both linear and nonlinear multivariate data analysis techniques, revealed specific metabolite changes associated with metastatic CRC, including increased levels of lactate, glutamate, and pyruvate, and decreased levels of certain amino acids and total fatty acids. Biomarker ratios such as glutamate-to-glutamine and pyruvate-to-alanine were also found to be related to CRC. The study also found that glutamate was linked to progression-free survival and that both glutamate and 3-hydroxybutyrate were risk factors for metastatic CRC. Additionally, gas chromatography coupled to flame-ionization detection was utilized to analyze the fatty acid profile and pathway analysis was performed on the profiled metabolites to understand the metabolic processes involved in CRC. A correlation was also found between the presence of certain metabolites in the blood of CRC patients and certain clinical features.
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Affiliation(s)
- Ana Isabel Tristán
- Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Almería, Spain
| | - Encarnación González-Flores
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain
- Medical Oncology Service, Virgen de las Nieves Hospital, Granada, Spain
| | - Ana Del Mar Salmerón
- Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Almería, Spain
| | - Ana Cristina Abreu
- Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Almería, Spain
| | - Octavio Caba
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Cristina Jiménez-Luna
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
| | - Consolación Melguizo
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
| | - José Prados
- Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Ignacio Fernández
- Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Almería, Spain
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10
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MicroRNA-122 in human cancers: from mechanistic to clinical perspectives. Cancer Cell Int 2023; 23:29. [PMID: 36803831 PMCID: PMC9940444 DOI: 10.1186/s12935-023-02868-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 02/09/2023] [Indexed: 02/22/2023] Open
Abstract
MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate the expression of target genes post-transcriptionally and interact with mRNA-coding genes. MiRNAs play vital roles in many biological functions, and abnormal miRNA expression has been linked to various illnesses, including cancer. Among the miRNAs, miR-122, miR-206, miR-21, miR-210, miR-223, and miR-424 have been extensively studied in various cancers. Although research in miRNAs has grown considerably over the last decade, much is yet to be discovered, especially regarding their role in cancer therapies. Several kinds of cancer have been linked to dysregulation and abnormal expression of miR-122, indicating that miR-122 may serve as a diagnostic and/or prognostic biomarker for human cancer. Consequently, in this review literature, miR-122 has been analyzed in numerous cancer types to sort out the function of cancer cells miR-122 and enhance patient response to standard therapy.
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11
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Fotakopoulos G, Georgakopoulou VE, Spandidos DA, Papalexis P, Angelopoulou E, Aravantinou-Fatorou A, Trakas N, Trakas I, Brotis AG. Role of miR‑200 family in brain metastases: A systematic review. Mol Clin Oncol 2023; 18:15. [PMID: 36798467 PMCID: PMC9926042 DOI: 10.3892/mco.2023.2611] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 01/18/2023] [Indexed: 01/26/2023] Open
Abstract
Brain metastasis (BM) represents the single most severe neurological complication of systemic cancer. The prognosis of patients with BM is poor, irrespective of the implemented treatment. The present study performed a systematic review of the literature using three online databases (PubMed, Scopus and Web of Science). Recently, a number of small RNA molecules, the microRNAs (miRNAs/miRs), have attracted increasing scientific attention. Members of the miR-200 family, which includes five miRNAs (miR-141, miR-200a, miR-200b, miR-200c and miR-429) appear to play pivotal roles in cancer initiation and metastasis. Indeed, a systematic review of the pertinent literature revealed that miR-200 family members regulate the brain metastatic cascade, particularly by modulating epithelial-to-mesenchymal transition. That holds true for the major representatives of BM, including lung and breast cancer, as well as for other less frequent secondary lesions originating from melanoma and the gastrointestinal tract. Therefore, the miRNAs may serve as potential diagnostic and/or prognostic markers, and under specific circumstances, as invaluable therapeutic targets. However, the available clinical evidence is relatively limited. A number of studies have suggested that the miR-200 family members are accurate prognostic markers of survival and resistance to chemotherapy in patients with breast cancer. Similarly, they may prove helpful in differentiating a metastatic lesion from a malignant glioma, or a hemangioblastoma from a renal cell carcinoma in patients with von Hippel Lindau syndrome, based on a cerebrospinal fluid sample. However, currently, there is no known therapeutic role for miR-200 family members in the setting of BM.
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Affiliation(s)
- George Fotakopoulos
- Department of Neurosurgery, General University Hospital of Larissa, 41221 Larissa, Greece,Correspondence to: Dr George Fotakopoulos, Department of Neurosurgery, General University Hospital of Larissa, Mezourlo, 41221 Larissa, Greece
| | - Vasiliki Epameinondas Georgakopoulou
- Department of Infectious Diseases and COVID-19 Unit, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Petros Papalexis
- Unit of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece,Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece
| | - Efthalia Angelopoulou
- Department of Neurology, Eginitio University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Aikaterini Aravantinou-Fatorou
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Nikolaos Trakas
- Department of Biochemistry, Sismanogleio Hospital, 15126 Athens, Greece
| | - Ilias Trakas
- Department of Infectious Diseases and COVID-19 Unit, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Alexandros G. Brotis
- Department of Neurosurgery, General University Hospital of Larissa, 41221 Larissa, Greece
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12
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Ganesan H, Nandy SK, Banerjee A, Pathak S, Zhang H, Sun XF. RNA-Interference-Mediated miR-122-Based Gene Regulation in Colon Cancer, a Structural In Silico Analysis. Int J Mol Sci 2022; 23:ijms232315257. [PMID: 36499586 PMCID: PMC9739210 DOI: 10.3390/ijms232315257] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/18/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
The role of microRNA 122 (miR-122) in colorectal cancer (CRC) has not been widely investigated. In the current study, we aimed to identify the prominent gene and protein interactors of miR122 in CRC. Based on their binding affinity, these targets were chosen as candidate genes for the creation of miR122-mRNA duplexes. Following this, we examined the miRNA-mediated silencing mechanism using the gene-silencing complex protein Argonaute (AGO). Public databases, STRING, and GeneMANIA were utilized to identify major proteins and genes interacting with miR-122. DAVID, PANTHER, UniProt, FunRich, miRwalk, and KEGG were used for functional annotation, pathway enrichment, binding affinity analysis, and expression of genes in different stages of cancer. Three-dimensional duplexes of hub genes and miR-122 were created using the RNA composer, followed by molecular interaction analysis using molecular docking with the AGO protein. We analyzed, classified, and scrutinized 93 miR-122 interactors using various bioinformatic approaches. A total of 14 hub genes were categorized as major interactors of miR-122. The study confirmed the role of various experimentally documented miR-122 interactors such as MTDH (Q86UE4), AKT1 (P31749), PTPN1 (P18031), MYC (P01106), GSK3B (P49841), RHOA (P61586), and PIK3CG (P48736) and put forth several novel interactors, with AKT3 (Q9Y243), NCOR2 (Q9Y618), PIK3R2 (O00459), SMAD4 (P61586), and TGFBR1 (P36897). Double-stranded RNA duplexes of the strongest interactors were found to exhibit higher binding affinity with AGO. In conclusions, the study has explored the role of miR-122 in CRC and has identified a closely related group of genes influencing the prognosis of CRC in multiple ways. Further, these genes prove to be targets of gene silencing through RNA interference and might serve as effective therapeutic targets in understanding and treating CRC.
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Affiliation(s)
- Harsha Ganesan
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Suman K. Nandy
- BioNEST Bioincubator Facility, North-Eastern Hill University, Tura Campus, Chasingre, Tura 793022, Meghalaya, India
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam, Chennai 603103, Tamil Nadu, India
- Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden
- Correspondence: (S.P.); (X.-F.S.)
| | - Hong Zhang
- School of Medical Sciences, Faculty of Medicine and Health, Orebro University, 702 81 Örebro, Sweden
| | - Xiao-Feng Sun
- Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden
- Correspondence: (S.P.); (X.-F.S.)
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13
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Volovat SR, Augustin I, Zob D, Boboc D, Amurariti F, Volovat C, Stefanescu C, Stolniceanu CR, Ciocoiu M, Dumitras EA, Danciu M, Apostol DGC, Drug V, Shurbaji SA, Coca LG, Leon F, Iftene A, Herghelegiu PC. Use of Personalized Biomarkers in Metastatic Colorectal Cancer and the Impact of AI. Cancers (Basel) 2022; 14:4834. [PMID: 36230757 PMCID: PMC9562853 DOI: 10.3390/cancers14194834] [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: 07/10/2022] [Revised: 09/18/2022] [Accepted: 09/29/2022] [Indexed: 12/09/2022] Open
Abstract
Colorectal cancer is a major cause of cancer-related death worldwide and is correlated with genetic and epigenetic alterations in the colonic epithelium. Genetic changes play a major role in the pathophysiology of colorectal cancer through the development of gene mutations, but recent research has shown an important role for epigenetic alterations. In this review, we try to describe the current knowledge about epigenetic alterations, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators and the prognostic and predictive biomarkers in metastatic colorectal disease that can allow increases in the effectiveness of treatments. Additionally, the intestinal microbiota's composition can be an important biomarker for the response to strategies based on the immunotherapy of CRC. The identification of biomarkers in mCRC can be enhanced by developing artificial intelligence programs. We present the actual models that implement AI technology as a bridge connecting ncRNAs with tumors and conducted some experiments to improve the quality of the model used as well as the speed of the model that provides answers to users. In order to carry out this task, we implemented six algorithms: the naive Bayes classifier, the random forest classifier, the decision tree classifier, gradient boosted trees, logistic regression and SVM.
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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 Iasi, Romania
| | - Iolanda Augustin
- Department of Medical Oncology, AI.Trestioreanu Institute of Oncology, 022328 Bucharest, Romania
| | - Daniela Zob
- Department of Medical Oncology, AI.Trestioreanu Institute of Oncology, 022328 Bucharest, Romania
| | - Diana Boboc
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
| | - Florin Amurariti
- Department of Medical Oncology-Radiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
| | - Constantin Volovat
- Department of Medical Oncology, “Euroclinic” Center of Oncology, 2 Vasile Conta Str., 700106 Iasi, Romania
| | - Cipriana Stefanescu
- Department of Biophysics and Medical Physics-Nuclear Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
| | - Cati Raluca Stolniceanu
- Department of Biophysics and Medical Physics-Nuclear Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
| | - Manuela Ciocoiu
- Department of Pathophysiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Eduard Alexandru Dumitras
- Department of Pathophysiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Department of Anesthesiology and Intensive Care, Regional Institute of Oncology, 700115 Iasi, Romania
| | - Mihai Danciu
- Pathology Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | | | - Vasile Drug
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University Str., 700115 Iasi, Romania
- Gastroenterology Clinic, Institute of Gastroenterology and Hepatology, ‘St. Spiridon’ Clinical Hospital, 700115 Iasi, Romania
| | - Sinziana Al Shurbaji
- Gastroenterology Clinic, Institute of Gastroenterology and Hepatology, ‘St. Spiridon’ Clinical Hospital, 700115 Iasi, Romania
| | - Lucia-Georgiana Coca
- Faculty of Computer Science, Alexandru Ioan Cuza University, 700115 Iasi, Romania
| | - Florin Leon
- Faculty of Automatic Control and Computer Engineering, Gheorghe Asachi Technical University, 700115 Iasi, Romania
| | - Adrian Iftene
- Faculty of Computer Science, Alexandru Ioan Cuza University, 700115 Iasi, Romania
| | - Paul-Corneliu Herghelegiu
- Faculty of Automatic Control and Computer Engineering, Gheorghe Asachi Technical University, 700115 Iasi, Romania
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14
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Xie X, Wang Y, Sheng N, Zhang S, Cao Y, Fu Y. Predicting miRNA-disease associations based on multi-view information fusion. Front Genet 2022; 13:979815. [PMID: 36238163 PMCID: PMC9552014 DOI: 10.3389/fgene.2022.979815] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/16/2022] [Indexed: 11/13/2022] Open
Abstract
MicroRNAs (miRNAs) play an important role in various biological processes and their abnormal expression could lead to the occurrence of diseases. Exploring the potential relationships between miRNAs and diseases can contribute to the diagnosis and treatment of complex diseases. The increasing databases storing miRNA and disease information provide opportunities to develop computational methods for discovering unobserved disease-related miRNAs, but there are still some challenges in how to effectively learn and fuse information from multi-source data. In this study, we propose a multi-view information fusion based method for miRNA-disease association (MDA)prediction, named MVIFMDA. Firstly, multiple heterogeneous networks are constructed by combining the known MDAs and different similarities of miRNAs and diseases based on multi-source information. Secondly, the topology features of miRNAs and diseases are obtained by using the graph convolutional network to each heterogeneous network view, respectively. Moreover, we design the attention strategy at the topology representation level to adaptively fuse representations including different structural information. Meanwhile, we learn the attribute representations of miRNAs and diseases from their similarity attribute views with convolutional neural networks, respectively. Finally, the complicated associations between miRNAs and diseases are reconstructed by applying a bilinear decoder to the combined features, which combine topology and attribute representations. Experimental results on the public dataset demonstrate that our proposed model consistently outperforms baseline methods. The case studies further show the ability of the MVIFMDA model for inferring underlying associations between miRNAs and diseases.
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Affiliation(s)
- Xuping Xie
- Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun, China
| | - Yan Wang
- Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun, China
- School of Artificial Intelligence, Jilin University, Changchun, China
- *Correspondence: Yan Wang,
| | - Nan Sheng
- Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun, China
| | - Shuangquan Zhang
- Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun, China
| | - Yangkun Cao
- School of Artificial Intelligence, Jilin University, Changchun, China
| | - Yuan Fu
- Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, United Kingdom
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15
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The role of MicroRNA networks in tissue-specific direct and indirect effects of metformin and its application. Biomed Pharmacother 2022; 151:113130. [PMID: 35598373 DOI: 10.1016/j.biopha.2022.113130] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/06/2022] [Accepted: 05/13/2022] [Indexed: 11/20/2022] Open
Abstract
Metformin is a first-line oral antidiabetic agent that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The specific regulatory details and mechanisms underlying these benefits are still unclear and require further investigation. There is recent mounting evidence that metformin has pleiotropic effects on the target tissue development in metabolic organs, including adipose tissue, the gastrointestinal tract and the liver. The mechanism of actions of metformin are divided into direct effects on target tissues and indirect effects via non-targeted tissues. MicroRNAs (miRNAs) are a class of endogenous, noncoding, negative gene regulators that have emerged as important regulators of a number of diseases, including type 2 diabetes mellitus (T2DM). Metformin is involved in many aspects of miRNA regulation, and metformin treatment in T2DM should be associated with other miRNA targets. A large number of miRNAs regulation by metformin in target tissues with either direct or indirect effects has gradually been revealed in the context of numerous diseases and has gradually received increasing attention. This paper thoroughly reviews the current knowledge about the role of miRNA networks in the tissue-specific direct and indirect effects of metformin. Furthermore, this knowledge provides a novel theoretical basis and suggests therapeutic targets for the clinical treatment of metformin and miRNA regulators in the prevention and treatment of cancer, cardiovascular disorders, diabetes and its complications.
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16
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Elrebehy MA, Al-Saeed S, Gamal S, El-Sayed A, Ahmed AA, Waheed O, Ismail A, El-Mahdy HA, Sallam AAM, Doghish AS. miRNAs as cornerstones in colorectal cancer pathogenesis and resistance to therapy: A spotlight on signaling pathways interplay - A review. Int J Biol Macromol 2022; 214:583-600. [PMID: 35768045 DOI: 10.1016/j.ijbiomac.2022.06.134] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/18/2022] [Accepted: 06/19/2022] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Consequently, dysregulation and disruption in their function, miRNAs are linked to CRC malignant pathogenesis by controlling several cellular processes involved in the CRC. These cellular processes include increased proliferative and invasive capacity, cell cycle aberration, evasion of apoptosis, enhanced EMT, promotion of angiogenesis and metastasis, and decreased sensitivity to major treatments. The miRNAs control cellular processes in CRC via regulation of pathways such as Wnt/β-catenin signaling, PTEN/AKT/mTOR axis, KRAS, TGFb signaling, VEGFR, EGFR, and P53. Hence, the goal of this review was to review miRNA biogenesis and present an updated summary of oncogenic and tumor suppressor (TS) miRNAs and their potential implication in CRC pathogenesis and responses to chemotherapy and radiotherapy. We also summarise the biological importance and clinical applications of miRNAs in the CRC.
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Affiliation(s)
- Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Sarah Al-Saeed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Sara Gamal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Asmaa El-Sayed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Alshaimaa A Ahmed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Omnia Waheed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry Department, Faculty of Pharmacy, Ain-Shams University, Abassia, Cairo 11566, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
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17
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Sundararajan V, Burk UC, Bajdak-Rusinek K. Revisiting the miR-200 Family: A Clan of Five Siblings with Essential Roles in Development and Disease. Biomolecules 2022; 12:biom12060781. [PMID: 35740906 PMCID: PMC9221129 DOI: 10.3390/biom12060781] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/29/2022] [Accepted: 06/01/2022] [Indexed: 12/07/2022] Open
Abstract
Over two decades of studies on small noncoding RNA molecules illustrate the significance of microRNAs (miRNAs/miRs) in controlling multiple physiological and pathological functions through post-transcriptional and spatiotemporal gene expression. Among the plethora of miRs that are essential during animal embryonic development, in this review, we elaborate the indispensable role of the miR-200 family (comprising miR-200a, -200b, 200c, -141, and -429) in governing the cellular functions associated with epithelial homeostasis, such as epithelial differentiation and neurogenesis. Additionally, in pathological contexts, miR-200 family members are primarily involved in tumor-suppressive roles, including the reversal of the cancer-associated epithelial–mesenchymal transition dedifferentiation process, and are dysregulated during organ fibrosis. Moreover, recent eminent studies have elucidated the crucial roles of miR-200s in the pathophysiology of multiple neurodegenerative diseases and tissue fibrosis. Lastly, we summarize the key studies that have recognized the potential use of miR-200 members as biomarkers for the diagnosis and prognosis of cancers, elaborating the application of these small biomolecules in aiding early cancer detection and intervention.
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Affiliation(s)
- Vignesh Sundararajan
- Cancer Science Institute of Singapore, National University of Singapore, Center for Translational Medicine, Singapore 117599, Singapore;
| | - Ulrike C. Burk
- Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany;
| | - Karolina Bajdak-Rusinek
- Department of Medical Genetics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
- Correspondence: ; Tel.: +48-32-208-8382
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18
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Yang F, Xuan G, Chen Y, Cao L, Zhao M, Wang C, Chen E. MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Colorectal Cancer. Front Cell Dev Biol 2022; 10:828128. [PMID: 35465317 PMCID: PMC9023807 DOI: 10.3389/fcell.2022.828128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common types of cancer and one of the leading causes of mortality worldwide. MicroRNAs (miRNAs) play central roles in normal cell maintenance, development, and other physiological processes. Growing evidence has illustrated that dysregulated miRNAs can participate in the initiation, progression, metastasis, and therapeutic resistance that confer miRNAs to serve as clinical biomarkers and therapeutic targets for CRC. Through binding to the 3′-untranslated region (3′-UTR) of target genes, miRNAs can lead to target mRNA degradation or inhibition at a post-transcriptional level. During the last decade, studies have found numerous miRNAs and their potential targets, but the complex network of miRNA/Targets in CRC remains unclear. In this review, we sought to summarize the complicated roles of the miRNA-target regulation network (Wnt, TGF-β, PI3K-AKT, MAPK, and EMT related pathways) in CRC with up-to-date, high-quality published data. In particular, we aimed to discuss the downstream miRNAs of specific pathways. We hope these data can be a potent supplement for the canonical miRNA-target regulation network.
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Affiliation(s)
- Fangfang Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
| | - Guoyun Xuan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi’an, China
| | - Yixin Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
| | - Lichao Cao
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
| | - Min Zhao
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
| | - Chen Wang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
| | - Erfei Chen
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, China
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi’an, China
- *Correspondence: Erfei Chen,
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19
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Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases. Int J Mol Sci 2022; 23:ijms23073683. [PMID: 35409043 PMCID: PMC8999078 DOI: 10.3390/ijms23073683] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/21/2022] [Accepted: 03/25/2022] [Indexed: 02/01/2023] Open
Abstract
Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.
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20
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Jorgensen BG, Ro S. MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets. Int J Mol Sci 2022; 23:2166. [PMID: 35216281 PMCID: PMC8876324 DOI: 10.3390/ijms23042166] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 01/28/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.
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Affiliation(s)
| | - Seungil Ro
- Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;
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21
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Gallbladder Cancer Cell-Derived Exosome-Mediated Transfer of Leptin Promotes Cell Invasion and Migration by Modulating STAT3-Mediated M2 Macrophage Polarization. Anal Cell Pathol 2022; 2022:9994906. [PMID: 35111566 PMCID: PMC8803447 DOI: 10.1155/2022/9994906] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 12/17/2021] [Accepted: 12/27/2021] [Indexed: 12/02/2022] Open
Abstract
Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.
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22
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Cavallari I, Ciccarese F, Sharova E, Urso L, Raimondi V, Silic-Benussi M, D’Agostino DM, Ciminale V. The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers. Cancers (Basel) 2021; 13:5874. [PMID: 34884985 PMCID: PMC8656820 DOI: 10.3390/cancers13235874] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/13/2022] Open
Abstract
The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.
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Affiliation(s)
- Ilaria Cavallari
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Francesco Ciccarese
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Evgeniya Sharova
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Loredana Urso
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padova, Italy
| | - Vittoria Raimondi
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Micol Silic-Benussi
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Donna M. D’Agostino
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Biomedical Sciences, University of Padua, 35131 Padova, Italy
| | - Vincenzo Ciminale
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padova, Italy
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23
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Chen W, Wang W. Serum hsa-miR-30e As a Potential Biomarker to Predict the Effect of Neoadjuvant Chemoradiation Therapy in Locally Advanced Rectal Cancer. Genet Test Mol Biomarkers 2021; 25:696-706. [PMID: 34788143 DOI: 10.1089/gtmb.2020.0300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective: To identify serum microRNAs (miRNAs) correlated with response to neoadjuvant chemoradiation therapy (NCRT) in locally advanced rectal cancer (LARC) patients using in silico analysis and laboratory validation studies. Methods: GSE68204 and GSE68204 data sets were analyzed to identify differentially expressed (DE) miRNAs in NCRT responders using the GEO2R Limma package within the R software suite. Then we used quantitative real-time polymerase chain reaction to detect the upregulated target miRNAs in the serum of 20 LARC patients. Logistic regression was used to evaluate the effect of serum miRNA level on response. Gene Ontology and pathway enrichment analyses were performed to predict the corresponding functions of the DE miRNAs. Correlation between the expression of the hub target genes and the abundance of tumor-infiltrating lymphocytes was further investigated. Results: hsa-miR-30e and hsa-miR-210 were verified to be upregulated in tumor tissues of NCRT responders. Subsequent liquid-biopsy studies revealed that the serum level of miR-30e was associated with a 2.47-fold increased incidence of NCRT-responsive patients in comparison with nonresponders (p-value = 0.038, Mann-Whitney test). Nine hub target genes of hsa-miR-30e were enriched in pathways including immune regulation. The expression of these hub target genes was correlated with abundance of tumor-infiltrating lymphocytes. Conclusion: In summary, hsa-miR-30e was determined to be upregulated in rectal cancer tissues of NCRT-responders. Further investigations showed that increased serum levels of hsa-miR-30e were associated with an effective NCRT response in LARC patients.
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Affiliation(s)
- Weiwei Chen
- Department of Clinical Medicine, Guizhou Medical University, Guiyang, China.,Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.,Department of Abdominal Oncology, Guizhou Cancer Hospital, Guiyang, China
| | - Wenling Wang
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.,Department of Abdominal Oncology, Guizhou Cancer Hospital, Guiyang, China
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24
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Moazzendizaji S, Sevbitov A, Ezzatifar F, Jalili HR, Aalii M, Hemmatzadeh M, Aslani S, Gholizadeh Navashenaq J, Safari R, Hosseinzadeh R, Rahmany MR, Mohammadi H. microRNAs: Small molecules with a large impact on colorectal cancer. Biotechnol Appl Biochem 2021; 69:1893-1908. [PMID: 34550619 DOI: 10.1002/bab.2255] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/03/2021] [Indexed: 12/23/2022]
Abstract
Colorectal cancer (CRC) accounts for one of the main cancer-related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF-β pathways, was clarified.
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Affiliation(s)
- Sahand Moazzendizaji
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Andrey Sevbitov
- Head of Department of Propaedeutics of Dental Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Fatemeh Ezzatifar
- Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hamid Reza Jalili
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Morteza Aalii
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Maryam Hemmatzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Roghaiyeh Safari
- Molecular and Cellular Epigenetics (GIGA), University of Liege, Sart-Tilman Liège, Belgium.,13. Molecular and Cellular Biology (TERRA), Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium
| | - Ramin Hosseinzadeh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Rahmany
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
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25
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Cervena K, Novosadova V, Pardini B, Naccarati A, Opattova A, Horak J, Vodenkova S, Buchler T, Skrobanek P, Levy M, Vodicka P, Vymetalkova V. Analysis of MicroRNA Expression Changes During the Course of Therapy In Rectal Cancer Patients. Front Oncol 2021; 11:702258. [PMID: 34540669 PMCID: PMC8444897 DOI: 10.3389/fonc.2021.702258] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/16/2021] [Indexed: 12/28/2022] Open
Abstract
MicroRNAs (miRNAs) regulate gene expression in a tissue-specific manner. However, little is known about the miRNA expression changes induced by the therapy in rectal cancer (RC) patients. We evaluated miRNA expression levels before and after therapy and identified specific miRNA signatures reflecting disease course and treatment responses of RC patients. First, miRNA expression levels were assessed by next-generation sequencing in two plasma samplings (at the time of diagnosis and a year after) from 20 RC patients. MiR-122-5p and miR-142-5p were classified for subsequent validation in plasma and plasma extracellular vesicles (EVs) on an independent group of RC patients (n=107). Due to the intrinsic high differences in miRNA expression levels between samplings, cancer-free individuals (n=51) were included in the validation phase to determine the baseline expression levels of the selected miRNAs. Expression levels of these miRNAs were significantly different between RC patients and controls (for all p <0.001). A year after diagnosis, miRNA expression profiles were significantly modified in patients responding to treatment and were no longer different from those measured in cancer-free individuals. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling (miR-122-5p: plasma: p=0.05, EVs: p=0.007; miR-142-5p: plasma: p=0.008). Besides, overexpression of miR-122-5p and miR-142-5p in RC cell lines inhibited cell growth and survival. This study provides novel evidence that circulating miR-122-5p and miR-142-5p have a high potential for RC screening and early detection as well as for the assessment of patients' outcomes and the effectiveness of treatment schedule.
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Affiliation(s)
- Klara Cervena
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia
| | - Vendula Novosadova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Prague, Czechia
| | - Barbara Pardini
- Molecular Genetics Epidemiology Unit, Italian Institute for Genomic Medicine, c/o IRCCS Candiolo,, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Alessio Naccarati
- Molecular Genetics Epidemiology Unit, Italian Institute for Genomic Medicine, c/o IRCCS Candiolo,, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Alena Opattova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Josef Horak
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Sona Vodenkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Tomas Buchler
- Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Pavel Skrobanek
- Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Miroslav Levy
- Department of Surgery, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czechia
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.,Institute of Biology and Medical Genetics, 1stMedical Faculty, Charles University, Prague, Czechia.,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
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26
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Maryam Khorasani, Shahbazi S, Abolhasani M, Shahrokh H, Mahdian R. Expression Profile of MiR-200 Family Members and Their Targets in Prostate Cancer. CYTOL GENET+ 2021. [DOI: 10.3103/s009545272104006x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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27
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Radwan E, Shaltout AS, Mansor SG, Shafik EA, Abbas WA, Shehata MR, Ali M. Evaluation of circulating microRNAs-211 and 25 as diagnostic biomarkers of colorectal cancer. Mol Biol Rep 2021; 48:4601-4610. [PMID: 34132944 DOI: 10.1007/s11033-021-06493-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 06/11/2021] [Indexed: 12/11/2022]
Abstract
Colorectal cancer is one of the most prevalent and deadly cancers worldwide. MicroRNAs are short single stranded non-coding RNAs that play important roles in carcinogenesis, tumor growth and tumor survival. Circulating microRNAs are increasingly becoming efficient and important biomarkers for several types of cancers. Herein, we aim to evaluate the diagnostic potentials of plasma microRNA-211 and microRNA-25 in colorectal cancer patients. Forty-four patients diagnosed with colorectal cancer and 40 healthy controls were recruited for the present study. Expressions of circulating microRNAs -211 and 25 were assessed by quantitative real-time polymerase chain reaction (RT-qPCR). Expression of transforming growth factor-beta, a key factor in tumorigenesis and a key inducer of epithelial to mesenchymal transition was assessed by enzyme-linked immunosorbent assay (ELISA) in patients' tissue and plasma. Our results demonstrated upregulated expressions of plasma microRNAs-211 and 25 correlated with the high transforming growth factor-beta (TGF-β1) expression in patients. In addition, plasma levels were positively correlated with lymph node metastasis. Moreover, receiver operating characteristic analysis demonstrated the reliability of microRNAs-211 and 25 for discriminating colorectal cancer patients from healthy individuals. MicroRNA-211 and microRNA-25 might have a tumorigenic role in colorectal cancer and their plasma levels could be potential biomarkers in its diagnosis.
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Affiliation(s)
- Eman Radwan
- Faculty of Medicine, Department of Medical Biochemistry, Assiut University, Assiut, 71515, Egypt.,Department of Biochemistry, Sphinx University, Assiut, Egypt
| | - Asmaa S Shaltout
- Faculty of Medicine, Department of Microbiology, Assiut University, Assiut, Egypt
| | - Shima Gafar Mansor
- Department of Oncological Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Engy A Shafik
- Department of Oncological Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Wael A Abbas
- Faculty of Medicine, Department of Internal Medicine, Assiut University, Assiut, Egypt
| | | | - Maha Ali
- Faculty of Medicine, Department of Medical Biochemistry, Assiut University, Assiut, 71515, Egypt.
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28
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Jimenez-Luna C, González-Flores E, Ortiz R, Martínez-González LJ, Antúnez-Rodríguez A, Expósito-Ruiz M, Melguizo C, Caba O, Prados J. Circulating PTGS2, JAG1, GUCY2C and PGF mRNA in Peripheral Blood and Serum as Potential Biomarkers for Patients with Metastatic Colon Cancer. J Clin Med 2021; 10:2248. [PMID: 34067294 PMCID: PMC8196898 DOI: 10.3390/jcm10112248] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/18/2021] [Accepted: 05/20/2021] [Indexed: 12/24/2022] Open
Abstract
Genes involved in the angiogenic process have been proposed for the diagnosis and therapeutic response of metastatic colorectal cancer (CRC). This study aimed to investigate the value of PTGS2, JAG1, GUCY2C and PGF-circulating RNA as biomarkers in metastatic CRC. Blood cells and serum mRNA from 59 patients with metastatic CRC and 47 healthy controls were analyzed by digital PCR. The area under the receiver operating characteristic curve (AUC) was used to estimate the diagnostic value of each mRNA alone or mRNA combinations. A significant upregulation of the JAG1, PTGS2 and GUCY2C genes in blood cells and serum samples from metastatic CRC patients was detected. Circulating mRNA levels in the serum of all genes were significantly more abundant than in blood. The highest discrimination ability between metastatic CRC patients and healthy donors was obtained with PTGS2 (AUC of 0.984) and GUCY2C (AUC of 0.896) in serum samples. Biomarker combinations did not improve the discriminatory capacity of biomarkers separately. Analyzed biomarkers showed no correlation with overall survival or progression-free survival, but GUCY2C and GUCY2C/PTGS2 expression in serum correlated significantly with the response to antiangiogenic agents. These findings demonstrate that assessment of genes involved in the angiogenic process may be a potential non-invasive diagnostic tool for metastatic CRC and its response to antiangiogenic therapy.
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Affiliation(s)
- Cristina Jimenez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; (C.J.-L.); (R.O.); (O.C.); (J.P.)
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
| | - Encarnación González-Flores
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
- Medical Oncology Service, Hospital Virgen de las Nieves, 18014 Granada, Spain
| | - Raul Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; (C.J.-L.); (R.O.); (O.C.); (J.P.)
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
| | - Luis J. Martínez-González
- GENyO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain; (L.J.M.-G.); (A.A.-R.)
| | - Alba Antúnez-Rodríguez
- GENyO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain; (L.J.M.-G.); (A.A.-R.)
| | - Manuela Expósito-Ruiz
- Unit of Biostatistics, Department of Statistics and Operations Research, School of Medicine, University of Granada, 18071 Granada, Spain;
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; (C.J.-L.); (R.O.); (O.C.); (J.P.)
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
| | - Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; (C.J.-L.); (R.O.); (O.C.); (J.P.)
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain; (C.J.-L.); (R.O.); (O.C.); (J.P.)
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain;
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29
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Bulfoni M, Pravisani R, Dalla E, Cesselli D, Hidaka M, Di Loreto C, Eguchi S, Baccarani U. miRNA expression profiles in liver grafts of HCV and HIV/HCV-infected recipients, 6 months after liver transplantation. J Med Virol 2021; 93:4992-5000. [PMID: 33818800 PMCID: PMC8360178 DOI: 10.1002/jmv.26999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 03/03/2021] [Accepted: 03/23/2021] [Indexed: 12/14/2022]
Abstract
In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co‐infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro‐fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR‐101, miR‐122, miR‐155, miR‐192, miR‐200c, miR‐338, and miR‐532 was determined by quantitative real‐time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV‐infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post‐LT. None of the patients was treated with direct‐acting anti‐HCV drugs. All co‐infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR‐101 (p = .03), miR‐122 (p = .012), and miR‐192 (p = .038) were significantly downregulated in HCV/HIV co‐infected and HCV mono‐infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co‐infected ones. Moreover, in co‐infected recipients but not in mono‐infected ones, miR‐101 inversely correlated with the peripheral HCV‐RNA levels (r = .41, p = .04) and miR‐122 inversely correlated with peripheral HCV‐RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02). In conclusion, as early as 6 months after LT, the presence of HIV‐HCV co‐infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.
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Affiliation(s)
| | - Riccardo Pravisani
- Department of Medicine, Liver-Kidney Transplant Unit, University of Udine, Udine, Italy
| | - Emiliano Dalla
- Department of Medicine, University of Udine, Udine, Italy
| | - Daniela Cesselli
- Department of Medicine, University of Udine, Udine, Italy.,Institute of Pathology, ASU FC, Udine, Italy
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Carla Di Loreto
- Department of Medicine, University of Udine, Udine, Italy.,Institute of Pathology, ASU FC, Udine, Italy
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Umberto Baccarani
- Department of Medicine, Liver-Kidney Transplant Unit, University of Udine, Udine, Italy
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30
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Alimoradi N, Firouzabadi N, Fatehi R. How metformin affects various malignancies by means of microRNAs: a brief review. Cancer Cell Int 2021; 21:207. [PMID: 33849540 PMCID: PMC8045276 DOI: 10.1186/s12935-021-01921-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 04/07/2021] [Indexed: 12/15/2022] Open
Abstract
Metformin known as the first-line orally prescribed drug for lowering blood glucose in type II diabetes (T2DM) has recently found various therapeutic applications including in cancer. Metformin has been studied for its influences in prevention and treatment of cancer through multiple mechanisms such as microRNA (miR) regulation. Alteration in the expression of miRs by metformin may play an important role in the treatment of various cancers. MiRs are single-stranded RNAs that are involved in gene regulation. By binding to the 3'UTR of target mRNAs, miRs influence protein levels. Irregularities in the expression of miRs that control the expression of oncogenes and tumor suppressor genes are associated with the onset and progression of cancer. Metformin may possess an effect on tumor prevention and progression by modifying miR expression and downstream pathways. Here, we summarize the effect of metformin on different types of cancer by regulating the expression of various miRs and the associated downstream molecules.
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Affiliation(s)
- Nahid Alimoradi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Firouzabadi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Reihaneh Fatehi
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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31
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Niu L, Yang W, Duan L, Wang X, Li Y, Xu C, Liu C, Zhang Y, Zhou W, Liu J, Zhao Q, Hong L, Fan D. Biological Implications and Clinical Potential of Metastasis-Related miRNA in Colorectal Cancer. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 23:42-54. [PMID: 33335791 PMCID: PMC7723777 DOI: 10.1016/j.omtn.2020.10.030] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC), ranking as the third commonest cancer, leads to extremely high rates of mortality. Metastasis is the major cause of poor outcome in CRC. When metastasis occurs, 5-year survival rates of patients decrease sharply, and strategies to enhance a patient's lifetime seem limited. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that are significantly involved in manipulation of CRC malignant phenotypes, including proliferation, invasion, and metastasis. To date, accumulating studies have revealed the mechanisms and functions of certain miRNAs in CRC metastasis. However, there is no systematic discussion about the biological implications and clinical potential (diagnostic role, prognostic role, and targeted therapy potential) of metastasis-related miRNAs in CRC. This review mainly summarizes the recent advances of miRNA-mediated metastasis in CRC. We also discuss the clinical values of metastasis-related miRNAs as potential biomarkers or therapeutic targets in CRC. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.
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Affiliation(s)
- Liaoran Niu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Wanli Yang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Lili Duan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Xiaoqian Wang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Yiding Li
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Chengchao Xu
- 94719 Military Hospital, Ji’an 343700, Jiangxi Province, China
| | - Chao Liu
- School of Basic Medical Sciences, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Yujie Zhang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Wei Zhou
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Jinqiang Liu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Qingchuan Zhao
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Liu Hong
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
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Dias F, Almeida C, Teixeira AL, Morais M, Medeiros R. LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression. Biomedicines 2021; 9:biomedicines9020195. [PMID: 33669301 PMCID: PMC7920065 DOI: 10.3390/biomedicines9020195] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/03/2021] [Accepted: 02/12/2021] [Indexed: 12/18/2022] Open
Abstract
The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.
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Affiliation(s)
- Francisca Dias
- Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center—LAB2, E Bdg 1st Floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal; (F.D.); (C.A.); (M.M.); (R.M.)
| | - Cristina Almeida
- Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center—LAB2, E Bdg 1st Floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal; (F.D.); (C.A.); (M.M.); (R.M.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvalação 6657, 4200-177 Porto, Portugal
| | - Ana Luísa Teixeira
- Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center—LAB2, E Bdg 1st Floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal; (F.D.); (C.A.); (M.M.); (R.M.)
- Correspondence: ; Tel.: +351-225084000 (ext. 5410)
| | - Mariana Morais
- Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center—LAB2, E Bdg 1st Floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal; (F.D.); (C.A.); (M.M.); (R.M.)
- Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center—LAB2, E Bdg 1st Floor, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal; (F.D.); (C.A.); (M.M.); (R.M.)
- Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvalação 6657, 4200-177 Porto, Portugal
- Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
- Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University (UFP), Praça 9 de Abril 349, 4249-004 Porto, Portugal
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Gao W, Chen Y, Yang J, Zhuo C, Huang S, Zhang H, Shi Y. Clinical Perspectives on Liquid Biopsy in Metastatic Colorectal Cancer. Front Genet 2021; 12:634642. [PMID: 33584829 PMCID: PMC7876389 DOI: 10.3389/fgene.2021.634642] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 01/04/2021] [Indexed: 02/05/2023] Open
Abstract
Liquid biopsy, which generally refers to the analysis of biological components such as circulating nuclear acids and circulating tumor cells in body fluids, particularly in peripheral blood, has shown good capacity to overcome several limitations faced by conventional tissue biopsies. Emerging evidence in recent decades has confirmed the promising role of liquid biopsy in the clinical management of various cancers, including colorectal cancer, which is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide. Despite the challenges and poor clinical outcomes, patients with metastatic colorectal cancer can expect potential clinical benefits with liquid biopsy. Therefore, in this review, we focus on the clinical prospects of liquid biopsy in metastatic colorectal cancer, specifically with regard to the recently discovered various biomarkers identified on liquid biopsy. These biomarkers have been shown to be potentially useful in multiple aspects of metastatic colorectal cancer, such as auxiliary diagnosis of metastasis, prognosis prediction, and monitoring of therapy response.
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Affiliation(s)
- Wei Gao
- Department of Internal Medicine-Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Yigui Chen
- Department of Internal Medicine-Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Jianwei Yang
- Department of Internal Medicine-Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Changhua Zhuo
- Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Sha Huang
- Department of Internal Medicine-Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Hui Zhang
- Department of Hepatopancreatobiliary Surgical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Yi Shi
- Department of Molecular Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
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Cai R, Lu Q, Wang D. Construction and prognostic analysis of miRNA-mRNA regulatory network in liver metastasis from colorectal cancer. World J Surg Oncol 2021; 19:7. [PMID: 33397428 PMCID: PMC7784011 DOI: 10.1186/s12957-020-02107-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 12/03/2020] [Indexed: 02/08/2023] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common cancers in the world, and liver metastasis is the leading cause of colorectal cancer-related deaths. However, the mechanism of liver metastasis in CRC has not been clearly elucidated. Methods Three datasets from the Gene Expression Omnibus (GEO) database were analyzed to obtain differentially expressed genes (DEGs), which were subjected to functional enrichment analysis and protein-protein interaction analysis. Subsequently, mRNA-miRNA network was constructed, and the associated DEGs and DEMs were performed for prognostic analysis. Finally, we did infiltration analysis of growth arrest specific 1 (GAS1)-associated immune cells. Results We obtained 325 DEGs and 9 differentially expressed miRNAs (DEMs) between primary CRC and liver metastases. Enrichment analysis and protein-protein interactions (PPI) further revealed the involvement of DEGs in the formation of the inflammatory microenvironment and epithelial-mesenchymal transition (EMT) during the liver metastases process in CRC. Survival analysis demonstrated that low-expressed GAS1 as well as low-expressed hsa-miR-33b-5p was a favorable prognostic indicator of overall survival. Further exploration of GAS1 revealed that its expression was interrelated with the infiltration of immune cells in tumor tissues. Conclusions In summary, DEGs, DEMs, and their interactions found in liver metastasis of CRC may provide a basis for further understanding of the mechanism of CRC metastasis.
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Affiliation(s)
- Ruyun Cai
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China
| | - Qian Lu
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China
| | - Da Wang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
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Yaghoubi N, Zahedi Avval F, Khazaei M, Aghaee-Bakhtiari SH. MicroRNAs as potential investigative and predictive biomarkers in colorectal cancer. Cell Signal 2020; 80:109910. [PMID: 33387618 DOI: 10.1016/j.cellsig.2020.109910] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/28/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is a noticeable reason of cancer-associated deaths with a high incidence and mortality rate. Countless effort have been put into the improving clinical management of CRC patients including more effective tools and a wide variety of biomarkers for diagnostic, prognostic or predictive purposes. In recent years, dysregulated miRNAs have been emerged as highly sensitive and specific markers to manage CRC in an effective way. They can play key roles in carcinogenesis as potential oncogenes, tumor suppressors or regulators of cancer network. Therefore, miRNAs may serve as molecular tools that can be quantified and used in diagnostic and prognostic approaches. Growing evidence also suggests that forced expression of tumor suppressor miRNAs or inhibiting the oncogene ones, can be used as a novel treatment strategy. In this review, we focus on the clinical applications of miRNAs as promising biomarkers of early cancer detection, prognosis and treatment.
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Affiliation(s)
- Neda Yaghoubi
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farnaz Zahedi Avval
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Hamid Aghaee-Bakhtiari
- Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Huang X, Zhu X, Yu Y, Zhu W, Jin L, Zhang X, Li S, Zou P, Xie C, Cui R. Dissecting miRNA signature in colorectal cancer progression and metastasis. Cancer Lett 2020; 501:66-82. [PMID: 33385486 DOI: 10.1016/j.canlet.2020.12.025] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 12/15/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer related deaths worldwide. Despite recent advancements in surgical and molecular targeted therapies that improved the therapeutic efficacy in CRC, the 5 years survival rate of CRC patients still remains frustratingly poor. Accumulated evidences indicate that microRNAs (miRNAs) play a crucial role in the progression and metastasis of CRC. Dysregulated miRNAs are closely associated with cancerous phenotypes (e.g. enhanced proliferative and invasive ability, evasion of apoptosis, cell cycle aberration, and promotion of angiogenesis) by regulating their target genes. In this review, we provide an updated overview of tumor suppressive and oncogenic miRNAs, circulatory miRNAs, and the possible causes of dysregulated miRNAs in CRC. In addition, we discuss the important functions of miRNAs in drug resistance of CRC.
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Affiliation(s)
- Xiangjie Huang
- Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Xinping Zhu
- Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Yun Yu
- Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Wangyu Zhu
- Affiliated Zhoushan Hospital, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Libo Jin
- Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China; Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, Zhejiang, 325035, China
| | - Xiaodong Zhang
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Shaotang Li
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Peng Zou
- Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China; Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, Zhejiang, 325035, China
| | - Congying Xie
- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Ri Cui
- Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, 325035, China; Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, Zhejiang, 325035, China.
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Cheng G, Li M, Ma X, Nan F, Zhang L, Yan Z, Li H, Zhang G, Han Y, Xie L, Guo X. Systematic Analysis of microRNA Biomarkers for Diagnosis, Prognosis, and Therapy in Patients With Clear Cell Renal Cell Carcinoma. Front Oncol 2020; 10:543817. [PMID: 33344224 PMCID: PMC7746831 DOI: 10.3389/fonc.2020.543817] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 11/03/2020] [Indexed: 12/11/2022] Open
Abstract
The ever-increasing morbidity and mortality of clear cell renal cell carcinoma (ccRCC) urgently demands updated biomarkers. MicroRNAs (miRNAs) are involved in diverse biological processes such as cell proliferation, differentiation, apoptosis by regulating their target genes' expression. In kidney cancers, miRNAs have been reported to be involved in tumorigenesis and to be the diagnostic, prognostic, and therapeutic response biomarkers. Here, we performed a systematic analysis for ccRCC-related miRNAs as biomarkers by searching keywords in the NCBI PubMed database and found 118 miRNAs as diagnostic biomarkers, 28 miRNAs as prognostic biomarkers, and 80 miRNAs as therapeutic biomarkers in ccRCC. miRNA-21, miRNA-155, miRNA-141, miRNA-126, and miRNA-221, as significantly differentially expressed miRNAs between cancer and normal tissues, play extensive roles in the cell proliferation, differentiation, apoptosis of ccRCC. GO and KEGG enrichment analysis of these miRNAs' target genes through Metascape showed these target genes are enriched in Protein Domain Specific Binding (GO:0019904). In this paper, we identified highly specific miRNAs in the pathogenesis of ccRCC and explored their potential applications for diagnosis, prognosis, and treatment of ccRCC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Longxiang Xie
- Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, Department of Preventive Medicine, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China
| | - Xiangqian Guo
- Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, Department of Preventive Medicine, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China
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Hazem RM, Mohamed AA, Ghareb N, Mehanna ET, Mesbah NM, Abo-Elmatty DM, Elgawish MS. Anti-cancer activity of two novel heterocyclic compounds through modulation of VEGFR and miR-122 in mice bearing Ehrlich ascites carcinoma. Eur J Pharmacol 2020; 892:173747. [PMID: 33232730 DOI: 10.1016/j.ejphar.2020.173747] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 11/02/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022]
Abstract
Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). Breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5 mg/kg and 10 mg/kg), (6&7) benzimidazotriazin treated (5 mg/kg and 10 mg/kg). The expression of miR-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum ALT, AST, creatinine, and urea were measured. Treatment with benzoimidazoquinazoline and benzimidazotriazin decreased tumor weight and serum levels of VEGF, and down-regulated expression of VEGFR2 and CD34 in the tumor tissue. miR-122 was upregulated, particularly in the benzimidazotriazin (10 mg/kg) group. Relative to cisplatin, the novel compounds were less toxic to kidneys. Benzoimidazoquinazoline and benzimidazotriazin are promising anti-cancer agents that act through inhibition of angiogenesis and thus provide a new strategy for advancement of chemotherapy.
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Affiliation(s)
- Reem M Hazem
- Department of Pharmacology, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Anhar A Mohamed
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Nagat Ghareb
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Eman T Mehanna
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Noha M Mesbah
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Dina M Abo-Elmatty
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Mohamed Saleh Elgawish
- Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt; Center for Molecular Spectroscopy and Dynamic, Institute for Basic Science, Korea University, Seoul, 02841, Republic of Korea.
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Curtaz CJ, Schmitt C, Blecharz-Lang KG, Roewer N, Wöckel A, Burek M. Circulating MicroRNAs and Blood-Brain-Barrier Function in Breast Cancer Metastasis. Curr Pharm Des 2020; 26:1417-1427. [PMID: 32175838 PMCID: PMC7475800 DOI: 10.2174/1381612826666200316151720] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 02/26/2020] [Indexed: 12/24/2022]
Abstract
Brain metastases are a major cause of death in breast cancer patients. A key event in the metastatic progression of breast cancer in the brain is the migration of cancer cells across the blood-brain barrier (BBB). The BBB is a natural barrier with specialized functions that protect the brain from harmful substances, including anti-tumor drugs. Extracellular vesicles (EVs) sequestered by cells are mediators of cell-cell communication. EVs carry cellular components, including microRNAs that affect the cellular processes of target cells. Here, we summarize the knowledge about microRNAs known to play a significant role in breast cancer and/or in the BBB function. In addition, we describe previously established in vitro BBB models, which are a useful tool for studying molecular mechanisms involved in the formation of brain metastases.
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Affiliation(s)
- Carolin J Curtaz
- Department of Gynecology and Obstetrics, University of Würzburg, Würzburg, Germany
| | - Constanze Schmitt
- Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany
| | - Kinga G Blecharz-Lang
- Department of Experimental Neurosurgery, Charite - Universitätsmedizin, Berlin, Germany
| | - Norbert Roewer
- Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany
| | - Achim Wöckel
- Department of Gynecology and Obstetrics, University of Würzburg, Würzburg, Germany
| | - Malgorzata Burek
- Department of Anaesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany
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Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-based Approach. Cancers (Basel) 2020; 12:cancers12113133. [PMID: 33114775 PMCID: PMC7692037 DOI: 10.3390/cancers12113133] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022] Open
Abstract
Robust non-invasive tests for prognostic stratification of bladder cancer (BCa) patients are in high demand. Following a comprehensive analysis of studies on BCa, we selected a panel of 29 microRNAs (miRNAs) and analyzed their levels in urine and plasma samples in a prospective cohort of 63 BCa patients (32 at high risk of recurrence and 31 low-risk cases) and 37 healthy controls using RT-qPCR. To design an assay suitable for large-scale testing, we applied a hierarchical pipeline to select the miRNAs that were not affected by confounding factors such as haematuria and urine specific gravity, and exceeded stringent cut-off criteria (fold change >2.5 and p-value < 0.005). Using a two-step decision tree based on the urine levels of miR-34a-5p, miR-200a-3p and miR-193a-5p, normalized against miR-125b-5p, patients could be classified as high- or low-risk with a sensitivity of 0.844, specificity of 0.806 and accuracy of 0.825. Furthermore, univariate Cox proportional hazards regression analyses indicated that increased urine levels of miR-29a-3p, miR-34a-5p, miR-193a-5p, miR-200c-3p, miR-205-5p and miR-532-5p were associated with a shorter event-free survival (hazard ratios > 3.1, p-value < 0.05). Taken together, our findings suggest that measuring the urine levels of these miRNAs could provide a novel cost-effective, noninvasive test for risk assessment of BCa patients.
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Yang Y, Meng WJ, Wang ZQ. MicroRNAs in Colon and Rectal Cancer - Novel Biomarkers from Diagnosis to Therapy. Endocr Metab Immune Disord Drug Targets 2020; 20:1211-1226. [PMID: 32370729 DOI: 10.2174/1871530320666200506075219] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/31/2020] [Accepted: 02/01/2020] [Indexed: 02/05/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a significant cause of tumor- related deaths worldwide. Traditional biomarkers, such as CEA and CA199, are not sensitive enough to provide useful information for early diagnosis and treatment and are rather used to track the clinical progression of the disease. There is growing evidence that microRNAs (miRNA) are potentially superior to traditional biomarkers as promising non-invasive biomarkers for the timely diagnosis and prediction of prognosis or treatment response in the management of CRC. In this review, the latest studies on the dysregulation of miRNAs expression in CRC and the potential for miRNAs to serve as biomarkers were collected. Given the limitations of miRNA, as discussed in this paper, its clinical applications as a diagnostic biomarker should be limited to use in combination with other biomarkers. Further research is necessary to elucidate the clinical applications of miRNA in therapy for CRC.
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Affiliation(s)
- Ying Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wen-Jian Meng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zi-Qiang Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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Yin W, Xu J, Li C, Dai X, Wu T, Wen J. Circular RNA circ_0007142 Facilitates Colorectal Cancer Progression by Modulating CDC25A Expression via miR-122-5p. Onco Targets Ther 2020; 13:3689-3701. [PMID: 32431519 PMCID: PMC7200250 DOI: 10.2147/ott.s238338] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/03/2020] [Indexed: 12/15/2022] Open
Abstract
Background Colorectal cancer (CRC) is a common malignant tumor in digestive system. Circular RNA (circRNA) circ_0007142 has been identified as an oncogene in CRC. However, the mechanism of circ_0007142 in CRC was rarely reported. Materials and Methods The levels of circ_0007142, dedicator of cytokinesis 1 (DOCK1), microRNA-122-5p (miR-122-5p), and cell division cycle 25A (CDC25A) in CRC tissues (n=31) and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and colony-forming ability were evaluated via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony-formation assay, respectively. The migrated and invaded abilities were monitored by Transwell assay. The dual-luciferase reporter assay was performed to validate the interactions between miR-122-5p and circ_0007142 or CDC25A. The protein level of CDC25A was detected via Western blot assay. The biological role of circ_0007142 was examined by xenograft tumor model in vivo. Results The levels of circ_0007142 and CDC25A were enhanced and the level of miR-122-5p was declined in CRC tissues and cells, while the level of DOCK1 had no fluctuation. Circ_0007142 sponged miR-122-5p and CDC25A was a target of miR-122-5p. Circ_0007142 knockdown impeded cell proliferation, colony formation, migration, and invasion in CRC cells by regulating miR-122-5p. Besides, miR-122-5p inhibitor promoted cell proliferation, colony formation, migration, and invasion in CRC cells by modulating CDC25A. Circ_0007142 regulated CDC25A expression in CRC cells by sponging miR-122-5p. Moreover, circ_0007142 knockdown blocked CRC tumor growth in vivo. Conclusion Circ_0007142 modulated CDC25A expression to promote CRC progression by sponging miR-122-5p.
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Affiliation(s)
- Wenzhe Yin
- Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
| | - Jun Xu
- Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
| | - Chao Li
- Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
| | - Xiankui Dai
- Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
| | - Tong Wu
- Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
| | - Jifeng Wen
- Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China
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Kunigenas L, Stankevicius V, Dulskas A, Budginaite E, Alzbutas G, Stratilatovas E, Cordes N, Suziedelis K. 3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment. Biomolecules 2020; 10:E613. [PMID: 32316138 PMCID: PMC7226077 DOI: 10.3390/biom10040613] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/05/2020] [Accepted: 04/13/2020] [Indexed: 01/21/2023] Open
Abstract
Altered expression of miRNAs in tumor tissue encourages the translation of this specific molecular pattern into clinical practice. However, the establishment of a selective biomarker signature for many tumor types remains an inextricable challenge. For this purpose, a preclinical experimental design, which could maintain a fast and sensitive discovery of potential biomarkers, is in demand. The present study suggests that the approach of 3D cell cultures as a preclinical cancer model that is characterized to mimic a natural tumor environment maintained in solid tumors could successfully be employed for the biomarker discovery and validation. Subsequently, in this study, we investigated an environment-dependent miRNA expression changes in colorectal adenocarcinoma DLD1 and HT29 cell lines using next-generation sequencing (NGS) technology. We detected a subset of 16 miRNAs differentially expressed in both cell lines cultivated in multicellular spheroids compared to expression levels in cells grown in 2D. Furthermore, results of in silico miRNA target analysis showed that miRNAs, which were differentially expressed in both cell lines grown in MCS, are involved in the regulation of molecular mechanisms implicated in cell adhesion, cell-ECM interaction, and gap junction pathways. In addition, integrins and platelet-derived growth factor receptors were determined to be the most significant target genes of deregulated miRNAs, which was concordant with the environment-dependent gene expression changes validated by RT-qPCR. Our results revealed that 3D microenvironment-dependent deregulation of miRNA expression in CRC cells potentially triggers essential molecular mechanisms predominantly including the regulation of cell adhesion, cell-cell, and cell-ECM interactions important in CRC initiation and development. Finally, we demonstrated increased levels of selected miR-142-5p in rectum tumor tissue samples after neoadjuvant long course treatment compared to miR-142-5p expression levels in tumor biopsy samples collected before the therapy. Remarkably, the elevation of miR-142-5p expression remained in tumor samples compared to adjacent normal rectum tissue as well. Therefore, the current study provides valuable insights into the molecular miRNA machinery of CRC and proposes a potential miRNA signature for the assessment of CRC in further clinical research.
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Affiliation(s)
- Linas Kunigenas
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
- Life Sciences Center, Institute of Biosciences, Vilnius University, LT-08412 Vilnius, Lithuania
| | - Vaidotas Stankevicius
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
- Life Sciences Center, Institute of Biotechnology, Vilnius University, LT-08412 Vilnius, Lithuania
| | - Audrius Dulskas
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LT-08406 Vilnius, Lithuania
- University of Applied Sciences, Faculty of Health Care, LT-08303 Vilnius, Lithuania
| | - Elzbieta Budginaite
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
| | - Gediminas Alzbutas
- Thermo Fisher Scientific, LT-02241 Vilnius, Lithuania;
- Institute of Informatics, Faculty of Mathematics and Informatics, Vilnius University, LT-08303 Vilnius, Lithuania
| | - Eugenijus Stratilatovas
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LT-08406 Vilnius, Lithuania
| | - Nils Cordes
- Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine, Technische Universität, D–01307 Dresden, Germany;
- Helmholtz–Zentrum Dresden–Rossendorf, Institute of Radiooncology–OncoRay, D–01328 Dresden, Germany
- German Cancer Consortium (DKTK), partner site Dresden, D–69192 Heidelberg, Germany
- German Cancer Research Center (DKFZ), D–69192 Heidelberg, Germany
| | - Kestutis Suziedelis
- National Cancer Institute, LT-08660 Vilnius, Lithuania; (L.K.); (A.D.); (E.B.); (E.S.)
- Life Sciences Center, Institute of Biosciences, Vilnius University, LT-08412 Vilnius, Lithuania
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Zhu J, Xu Y, Liu S, Qiao L, Sun J, Zhao Q. MicroRNAs Associated With Colon Cancer: New Potential Prognostic Markers and Targets for Therapy. Front Bioeng Biotechnol 2020; 8:176. [PMID: 32211396 PMCID: PMC7075808 DOI: 10.3389/fbioe.2020.00176] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 02/20/2020] [Indexed: 12/24/2022] Open
Abstract
MicroRNAs (miRNAs) are a kind of non-coding RNA (ncRNA) that regulate the expression of target genes and play a role in the occurrence and development of cancers. Colon cancer (COAD) is the second most common cause of cancer-related mortality. However, the prognostic value of miRNAs in COAD is still confusing. In this study, we obtain miRNAs and messenger RNAs (mRNAs) expression profiles of COAD from the Cancer Genome Atlas (TCGA) database. After preliminary data screening and preprocessing, we acquire the expression data of 894 miRNAs and 17,019 mRNAs. Then, compared with the normal samples, 39 upregulated miRNAs and 54 downregulated miRNAs are identified by differential expression analysis. Furthermore, we obtain 1,487 upregulated mRNAs and 2,847 downregulated mRNAs. We confirm nine key miRNAs related to the survival rate of COAD patients. Moreover, by using bioinformatics methods, we get 461 common genes from both the target genes of these nine key miRNAs and differentially expressed mRNAs. Through analyzing the protein-protein interaction (PPI) network of these 461 common genes and survival analysis, we confirm five hub genes as promising biomarkers for COAD prognosis. It is worth mentioning that no previous reports have found that PGR and KCNB1 are related to COAD. We expect these key miRNAs and hub genes will provide a new way for the study of COAD.
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Affiliation(s)
- Junfeng Zhu
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Ying Xu
- Office of Drug Clinical Trials, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Shanshan Liu
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Li Qiao
- Department of Clinical Laboratory, General Hospital of Northern Theater Command, Shenyang, China
| | - Jianqiang Sun
- School of Automation and Electrical Engineering, Linyi University, Linyi, China
| | - Qi Zhao
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China.,College of Computer Science, Shenyang Aerospace University, Shenyang, China
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45
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Peng Q, Cheng M, Li T, Chen X, Shen Y, Zhu Y, Xu B. Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer. Cancer Cell Int 2020; 20:56. [PMID: 32099529 PMCID: PMC7029504 DOI: 10.1186/s12935-020-1142-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 02/12/2020] [Indexed: 01/11/2023] Open
Abstract
Background Accumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial. Methods We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC. Results Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01–1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein‑protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC. Conclusions Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
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Affiliation(s)
- Qiliang Peng
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Ming Cheng
- 3Department of General Surgery, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China
| | - Ting Li
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Xiangying Chen
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yi Shen
- 4Department of Radiation Oncology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Yaqun Zhu
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Bo Xu
- 3Department of General Surgery, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China
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Zhou Q, Perakis SO, Ulz P, Mohan S, Riedl JM, Talakic E, Lax S, Tötsch M, Hoefler G, Bauernhofer T, Pichler M, Gerger A, Geigl JB, Heitzer E, Speicher MR. Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer. Genome Med 2020; 12:20. [PMID: 32087735 PMCID: PMC7036260 DOI: 10.1186/s13073-020-0719-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 01/31/2020] [Indexed: 02/08/2023] Open
Abstract
Background Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are largely unknown. Here, we employed whole-genome sequencing of plasma DNA to evaluate the tumor genome of patients undergoing treatment with bevacizumab to determine novel aberrations associated with resistance. Methods Using longitudinal plasma analyses, we studied the evolution of tumor genomes in a mCRC cohort (n = 150) and conducted analyses of CRC cases from The Cancer Genome Atlas (TCGA) database (n = 619) to identify associations between genomic aberrations and clinical features. We employed whole-genome sequencing to identify the most frequently occurring focal somatic copy number alterations (SCNAs). Using the TCGA data as a comparative and supporting dataset, we defined the minimally amplified overlapping region and studied the mechanistic consequences of copy number gain of the involved genes in this segment. In addition, we established an in vitro cell model and conducted downstream gene expression and cell viability assays to confirm our findings from the patient dataset. Results We observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of CRC cases from the TCGA database suggested that this amplicon is associated with more advanced stages. We confirmed that this 13q12.2 amplicon frequently emerges later during the clinical course of disease. After defining the minimally amplified region, we observed that the amplification and expression of one gene, POLR1D, impacted cell proliferation and resulted in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab treatment. In fact, in several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with therapy resistance. Conclusions Non-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients.
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Affiliation(s)
- Qing Zhou
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria
| | - Samantha O Perakis
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria
| | - Peter Ulz
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.,Present address: Freenome, South San Francisco, CA, USA
| | - Sumitra Mohan
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.,Present address: Cancer Research UK-Manchester Institute, Manchester, UK
| | - Jakob M Riedl
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
| | - Emina Talakic
- Division of General Radiology, Medical University of Graz, Graz, Austria
| | - Sigurd Lax
- Department of Pathology, General Hospital Graz II, Graz, Austria.,Johannes Kepler University Linz, Linz, Austria
| | - Martin Tötsch
- Institute of Pathology, General Hospital Hochsteiermark, Leoben, Austria
| | - Gerald Hoefler
- Institute of Pathology, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria
| | - Thomas Bauernhofer
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
| | - Martin Pichler
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
| | - Armin Gerger
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
| | - Jochen B Geigl
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria
| | - Ellen Heitzer
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria.,BioTechMed-Graz, Graz, Austria.,Christian Doppler Laboratory for Liquid Biopsies for Early Detection of Cancer, Graz, Austria
| | - Michael R Speicher
- Institute of Human Genetics, Diagnostic and Research Center for Molecular Biomedicine, Medical University of Graz, Graz, Austria. .,BioTechMed-Graz, Graz, Austria.
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Sun L, Liu X, Pan B, Hu X, Zhu Y, Su Y, Guo Z, Zhang G, Xu M, Xu X, Sun H, Wang S. Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis. J Cancer 2020; 11:630-637. [PMID: 31942186 PMCID: PMC6959047 DOI: 10.7150/jca.33022] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 08/29/2019] [Indexed: 12/16/2022] Open
Abstract
Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni- and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.
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Affiliation(s)
- Li Sun
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiangxiang Liu
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Bei Pan
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiuxiu Hu
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yefei Zhu
- Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yingying Su
- Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhirui Guo
- Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Guoying Zhang
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Mu Xu
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xueni Xu
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Huiling Sun
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shukui Wang
- Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
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MiR-200 family and cancer: From a meta-analysis view. Mol Aspects Med 2019; 70:57-71. [DOI: 10.1016/j.mam.2019.09.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 09/12/2019] [Accepted: 09/17/2019] [Indexed: 12/20/2022]
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Wang S, Zheng W, Ji A, Zhang D, Zhou M. Overexpressed miR-122-5p Promotes Cell Viability, Proliferation, Migration And Glycolysis Of Renal Cancer By Negatively Regulating PKM2. Cancer Manag Res 2019; 11:9701-9713. [PMID: 31814765 PMCID: PMC6863119 DOI: 10.2147/cmar.s225742] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 10/25/2019] [Indexed: 12/27/2022] Open
Abstract
Objective Renal cancer is one of the most deadly urological malignancies. Currently, there is still a lack of effective treatment. Our purpose was to explore the mechanisms of miR-122-5p in renal cancer. Methods The expression levels of miR-122-5p and pyruvate kinase M2 (PKM2) in renal cancer cells were detected by RT-qPCR and Western blot analyses, respectively. Then, we measured the cell viability after knockdown of miR-122-5p and PKM2 using CCK-8 assay. Moreover, flow cytometry was used to investigate cell cycle and apoptosis of renal cancer cells. The cell migration of renal cancer cells transfected by miR-122-5p inhibitor and siPKM2 was then detected by wound healing assay. Furthermore, glucose consumption and lactate production were measured. Autophagy-related protein LCII/I was detected by Western blot. Results MiR-122-5p was upregulated in renal cancer cells compared to HK2 cells, especially in 786-O cells. We found that silencing miR-122-5p promoted PKM2 expression in 786-O cells. After transfection of siPKM2 or miR-122-5p inhibitor, the cell viability of 786-O cells was significantly reduced. Furthermore, the G1 phase of 786-O cells was significantly blocked, and the S phase was significantly increased. In addition, knockdown of miR-122-5p or PKM2 promoted renal cancer cell apoptosis and inhibited cell migration. Glucose consumption of 786-O cells was significantly increased after transfection by siPKM2. Silencing miR-122-5p significantly promoted the expression levels of LCII/I. Conclusion Our findings revealed that overexpressed miR-122-5p promotes renal cancer cell viability, proliferation, migration, glycolysis and autophagy by negatively regulating PKM2, which provide a new insight for the development of renal cancer therapy.
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Affiliation(s)
- Shuai Wang
- Department of Urology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Wei Zheng
- Department of Urology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Alin Ji
- Department of Urology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Dahong Zhang
- Department of Urology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
| | - Mi Zhou
- Department of Urology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People's Republic of China
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Sun L, Chen T, Li T, Yu J. LncRNA IUR downregulates ZEB1 by upregulating miR-200 to inhibit prostate carcinoma. Physiol Genomics 2019; 51:607-611. [PMID: 31545930 DOI: 10.1152/physiolgenomics.00062.2019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
We in this study investigated the role of imatinib-upregulated lncRNA (IUR) in prostate carcinoma (PC). We observed that IUR was downregulated in PC, and its expression levels decreased with the increase of clinical stages. In PC tissues, microRNA (miR)-200 was positively, while ZEB1 was inversely correlated with IUR. In PC cells, IUR and miR-200 overexpression mediated the downregulated ZEB1. IUR overexpression mediated the upregulation of miR-200, while IUR expression was not significantly affected by miR-200 overexpression. Cell invasion and migration analysis showed that IUR and miR-200 overexpression resulted in decreased invasion and migration rates. ZEB1 overexpression played an opposite role and attenuated the effects of IUR and miR-200 overexpression. Therefore, IUR can downregulate ZEB1 by upregulating miR-200 to inhibit PC cell invasion and migration.
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Affiliation(s)
- Lingjun Sun
- Urology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China
| | - Taowei Chen
- Urology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China
| | - Tao Li
- Urology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China
| | - Jianda Yu
- Urology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China
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