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Zhang N, Liu Q, Wang D, Wang X, Pan Z, Han B, He G. Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy. Biomark Res 2025; 13:49. [PMID: 40134029 PMCID: PMC11934519 DOI: 10.1186/s40364-025-00759-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 03/05/2025] [Indexed: 03/27/2025] Open
Abstract
Galectins play pivotal roles in cellular recognition and signaling processes by interacting with glycoconjugates. Extensive research has highlighted the significance of Galectins in the context of cancer, aiding in the identification of biomarkers for early detection, personalized therapy, and predicting treatment responses. This review offers a comprehensive overview of the structural characteristics, ligand-binding properties, and interacting proteins of Galectins. We delve into their biological functions and examine their roles across various cancer types. Galectins, characterized by a conserved carbohydrate recognition domain (CRD), are divided into prototype, tandem-repeat, and chimera types based on their structural configurations. Prototype Galectins contain a single CRD, tandem-repeat Galectins contain two distinct CRDs linked by a peptide, and the chimera-type Galectin-3 features a unique structural arrangement. The capacity of Galectins to engage in multivalent interactions allows them to regulate a variety of signaling pathways, thereby affecting cell fate and function. In cancer, Galectins contribute to tumor cell transformation, angiogenesis, immune evasion, and metastasis, making them critical targets for therapeutic intervention. This review discusses the multifaceted roles of Galectins in cancer progression and explores current advancements in the development of Galectin-targeted therapies. We also address the challenges and future directions for integrating Galectin research into clinical practice to enhance cancer treatment outcomes. In brief, understanding the complex functions of Galectins in cancer biology opens new avenues for therapeutic strategies. Continued research on Galectin interactions and their pathological roles is essential for developing effective carbohydrate-based treatments and improving clinical interventions for cancer patients.
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Affiliation(s)
- Nan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology and School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China
| | - Qiao Liu
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China
| | - Daihan Wang
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiaoyun Wang
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China
| | - Zhaoping Pan
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China
| | - Bo Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology and School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Gu He
- Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
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Gurav MJ, Manasa J, Sanji AS, Megalamani PH, Chachadi VB. Lectin-glycan interactions: a comprehensive cataloguing of cancer-associated glycans for biorecognition and bio-alteration: a review. Glycoconj J 2024; 41:301-322. [PMID: 39218819 DOI: 10.1007/s10719-024-10161-y] [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: 06/03/2024] [Revised: 07/13/2024] [Accepted: 07/22/2024] [Indexed: 09/04/2024]
Abstract
This comprehensive review meticulously compiles data on an array of lectins and their interactions with different cancer types through specific glycans. Crucially, it establishes the link between aberrant glycosylation and cancer types. This repository of lectin-defined glycan signatures, assumes paramount importance in the realm of cancer and its dynamic nature. Cancer, known for its remarkable heterogeneity and individualized behaviour, can be better understood through these glycan signatures. The current review discusses the important lectins and their carbohydrate specificities, especially recognizing glycans of cancer origin. The review also addresses the key aspects of differentially expressed glycans on normal and cancerous cell surfaces. Specific cancer types highlighted in this review include breast cancer, colon cancer, glioblastoma, cervical cancer, lung cancer, liver cancer, and leukaemia. The glycan profiles unveiled through this review hold the key to tailor-made treatment and precise diagnostics. It opens up avenues to explore the potential of targeting glycosyltransferases and glycosidases linked with cancer advancement and metastasis. Armed with knowledge about specific glycan expressions, researchers can design targeted therapies to modulate glycan profiles, potentially hampering the advance of this relentless disease.
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Affiliation(s)
- Maruti J Gurav
- Post Graduate Department of Studies in Biochemistry, Karnatak University Dharwad, Dharwad, Karnataka, India
| | - J Manasa
- Post Graduate Department of Studies in Biochemistry, Karnatak University Dharwad, Dharwad, Karnataka, India
| | - Ashwini S Sanji
- Post Graduate Department of Studies in Biochemistry, Karnatak University Dharwad, Dharwad, Karnataka, India
| | - Prasanna H Megalamani
- Post Graduate Department of Studies in Biochemistry, Karnatak University Dharwad, Dharwad, Karnataka, India
| | - Vishwanath B Chachadi
- Post Graduate Department of Studies in Biochemistry, Karnatak University Dharwad, Dharwad, Karnataka, India.
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Lin L, Yu H, Xie X, Lei Q, Chen X, Su X, Wang X, Zhang S, Yang W. Leveraging FAM features to predict the prognosis of LGG patients and immunotherapy outcome. Am J Cancer Res 2024; 14:2731-2754. [PMID: 39005680 PMCID: PMC11236777 DOI: 10.62347/gigo3446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/27/2024] [Indexed: 07/16/2024] Open
Abstract
Heterogeneity at biological and transcriptomic levels poses a challenge in defining and typing low-grade glioma (LGG), leading to a critical need for specific molecular signatures to enhance diagnosis, therapy, and prognostic evaluation of LGG. This study focused on fatty acid metabolism (FAM) related genes and prognostic features to investigate the mechanisms and treatment strategies for LGG cell metastasis and invasion. By screening 158 FAM-related genes and clustering 512 LGG samples into two subtypes (C1 and C2), differential gene expression analysis and functional enrichment were performed. The immune cell scores and prognosis were compared between the two subtypes, with C1 showing poorer outcomes and higher immune scores. A four-gene signature (PHEX, SHANK2, HOPX, and LGALS1) was identified and validated across different datasets, demonstrating a stable predictive effect. Cellular experiments confirmed the roles of LGALS1 and HOPX in promoting tumor cell proliferation, migration, and invasion, while SHANK2 exhibited a suppressive effect. This four-gene signature based on FAM-related genes offers valuable insights for understanding the pathogenesis and clinical management of LGG.
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Affiliation(s)
- Liangbin Lin
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
- Obesity and Metabolism Medicine-Engineering Integration Laboratory, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University Chengdu 610031, The People's Republic of China
- The Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University Chengdu 610031, The People's Republic of China
| | - Hui Yu
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
| | - Xuelu Xie
- Department of Ophthalmology, West China School of Public Health and West China Forth Hospital, Sichuan University Chengdu 610041, Sichuan, The People's Republic of China
| | - Qingqiang Lei
- Center of Bone Metabolism and Repair, Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University Chongqing 400000, The People's Republic of China
| | - Xuerui Chen
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
| | - Xu Su
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
- College of Medicine, Southwest Jiaotong University Chengdu 610031, Sichuan, The People's Republic of China
| | - Xiuxuan Wang
- Department of Research and Development, Beijing DCTY Biotech Co., Ltd. Beijing 102200, The People's Republic of China
| | - Sunfu Zhang
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
| | - Wenyong Yang
- Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China
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Huang X, Yi G, Xu J, Gou S, Chen H, Chen X, Quan X, Xie L, Teichmann AT, Yang G, Chi H, Wang Q. Angiogenesis-related lncRNAs index: A predictor for CESC prognosis, immunotherapy efficacy, and chemosensitivity. J Cancer 2024; 15:3095-3113. [PMID: 38706901 PMCID: PMC11064265 DOI: 10.7150/jca.94332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/26/2024] [Indexed: 05/07/2024] Open
Abstract
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common gynecologic tumor and patients with advanced and recurrent disease usually have a poor clinical outcome. Angiogenesis is involved in the biological processes of tumors and can promote tumor growth and invasion. In this paper, we created a signature for predicting prognosis based on angiogenesis-related lncRNAs (ARLs). This provides a prospective direction for enhancing the efficacy of immunotherapy in CESC patients. We screened seven OS-related ARLs by univariate and multivariate regression analyses and Lasso analysis and developed a prognostic signature at the same time. Then, we performed an internal validation in the TCGA-CESC cohort to increase the precision of the study. In addition, we performed a series of analyses based on ARLs, including immune cell infiltration, immune function, immune checkpoint, tumor mutation load, and drug sensitivity analysis. Our created signature based on ARLs can effectively predict the prognosis of CESC patients. To strengthen the prediction accuracy of the signature, we built a nomogram by combining signature and clinical features.
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Affiliation(s)
- Xueyuan Huang
- Clinical Medical College, Southwest Medical University, Luzhou 646000, China
| | - Guangming Yi
- Department of Oncology, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan 621000, China
| | - Jiayu Xu
- School of Science, Minzu University of China, Beijing 100081, China
| | - Siqi Gou
- Clinical Medical College, Southwest Medical University, Luzhou 646000, China
| | - Haiqing Chen
- Clinical Medical College, Southwest Medical University, Luzhou 646000, China
| | - Xiaoyan Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, China
| | - Xiaomin Quan
- Beijing University of Chinese Medicine, 100029, Beijing, China
- Department of Oncology, Beijing University of Chinese Medicine second affiliated Dong Fang hospital, 100078, Beijing, China
| | - Linjia Xie
- Clinical Medical College, Southwest Medical University, Luzhou 646000, China
| | - Alexander Tobias Teichmann
- Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Guanhu Yang
- Department of Specialty Medicine, Ohio University, Athens 45701, OH, United States
| | - Hao Chi
- Clinical Medical College, Southwest Medical University, Luzhou 646000, China
| | - Qin Wang
- Sichuan Provincial Center for Gynecology and Breast Diseases (Gynecology), Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
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Zhang H, Wang J, Yang J, He Q, Guan S, Qiao M, Zhao J, Wang X. TMEM33 as a Prognostic Biomarker of Cervical Cancer and Its Correlation with Immune Infiltration. Mediators Inflamm 2023; 2023:5542181. [PMID: 37273452 PMCID: PMC10239303 DOI: 10.1155/2023/5542181] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/12/2023] [Accepted: 05/15/2023] [Indexed: 06/06/2023] Open
Abstract
In women all over the world, cervical cancer (CC) ranks as the fourth most common form of cancer to be diagnosed. It was previously reported that transmembrane protein 33(TMEM33) could report a poor prognosis in several cancers. The current study is aimed at investigating the potential prognostic value of TMEM33 and its relevance to the tumor microenvironment in CC in a comprehensive manner. In this study, CC specimens presented noticeably higher TMEM33 expression level in comparison to nontumor specimens. In pan-cancer assays, it was found that TMEM33 was present at a high level in many different kinds of tumors. We found that patients with CC patients who had a high TMEM33 expression presented worse overall survival (OS) and disease-free survival (DFS) relative to patients who had a low TMEM33 expression. According to the results of a multivariate analysis, a high level of TMEM33 expression can significantly and independently predict the prognosis of CC. The levels of TMEM33 were found to have a negative correlation with resting dendritic cells, resting mast cells, plasma cells, T cells CD8, T cells regulatory, and regulatory T cells. Finally, we confirmed that TMEM33 was overexpressed in CC cells, and its knockdown distinctly suppressed the proliferation and invasion of CC cells. Overall, we provided evidences that TMEM33 could be used as a potential biomarker to assess the prognosis and the level of immune infiltration in CC.
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Affiliation(s)
- Hui Zhang
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Jun Wang
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Ji Yang
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Qingwen He
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Sanli Guan
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Minxia Qiao
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Jian Zhao
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Xiu Wang
- Department of Ultrasound, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
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Shen L, Li Y, Hu G, Song X, Wang X, Li X, Xu X. Astragaloside IV suppresses the migration and EMT progression of cervical cancer cells by inhibiting macrophage M2 polarization through TGFβ/Smad2/3 signaling. Funct Integr Genomics 2023; 23:133. [PMID: 37081108 DOI: 10.1007/s10142-023-01017-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/02/2023] [Accepted: 03/06/2023] [Indexed: 04/22/2023]
Abstract
Cervical cancer (CC) is a gynecological malignant tumor worldwide. Astragaloside IV (AS-IV) has been found to exert antitumor effects on CC. In addition, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), play an important role in promoting cancer cell growth and angiogenesis. Thus, we explored the association between the antitumor effect of AS-IV and macrophage polarization in CC. Flow cytometry, ELISA, and RT‒qPCR assays were applied to detect the levels of CD163, IL-10, TGFβ, and CD206 in M2 macrophages with or without AS-IV treatment. In addition, conditioned medium (CM) was collected from these M2 macrophages, and CC cells were then cultured in various CMs. Wound healing and transwell assays were used to assess the migratory ability of CC cells. In this study, we found that AS-IV significantly inhibited M2 polarization of macrophages, as shown by decreased CD163, IL-10, TGFβ, and CD206 expression. In addition, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages notably inhibited angiogenesis, migration, and epithelial-mesenchymal transition (EMT) in CC cells. Furthermore, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages markedly reduced p-Smad2 and p-Smad3 protein expression in CC cells, and these changes were reversed by TGF-β treatment. Collectively, suppression of M2-like polarization of macrophages by AS-IV could prevent the migration and EMT of CC cells by inactivating TGF-β/Smad2/3 signaling. These findings might provide some theoretical support for exploring novel treatments for CC.
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Affiliation(s)
- Ling Shen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Jinping District, Shantou, 515041, Guangdong, China
| | - Yuancheng Li
- Department of Gynecology, Cancer Hospital Affiliated to Shantou University Medical College, Shantou, Guangdong, China
| | - Guiying Hu
- Department of Gynecology, Guangdong Maternal and Child Health Hospital, Guangzhou, Guangdong, China
| | - Xinli Song
- Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong, China
| | - Xiaoshuang Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Jinping District, Shantou, 515041, Guangdong, China
| | - Xiaoqi Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Jinping District, Shantou, 515041, Guangdong, China
| | - Xiaoyuan Xu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Jinping District, Shantou, 515041, Guangdong, China.
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Avila JP, Carvalho BM, Coimbra EC. A Comprehensive View of the Cancer-Immunity Cycle (CIC) in HPV-Mediated Cervical Cancer and Prospects for Emerging Therapeutic Opportunities. Cancers (Basel) 2023; 15:1333. [PMID: 36831674 PMCID: PMC9954575 DOI: 10.3390/cancers15041333] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/13/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC is persistent infection by a sexually transmitted virus, the human papillomavirus (HPV). Conventional treatments to eradicate this type of cancer are accompanied by high rates of resistance and a large number of side effects. Hence, it is crucial to devise novel effective therapeutic strategies. In recent years, an increasing number of studies have aimed to develop immunotherapeutic methods for treating cancer. However, these strategies have not proven to be effective enough to combat CC. This means there is a need to investigate immune molecular targets. An adaptive immune response against cancer has been described in seven key stages or steps defined as the cancer-immunity cycle (CIC). The CIC begins with the release of antigens by tumor cells and ends with their destruction by cytotoxic T-cells. In this paper, we discuss several molecular alterations found in each stage of the CIC of CC. In addition, we analyze the evidence discovered, the molecular mechanisms and their relationship with variables such as histological subtype and HPV infection, as well as their potential impact for adopting novel immunotherapeutic approaches.
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Affiliation(s)
| | | | - Eliane Campos Coimbra
- Institute of Biological Sciences, University of Pernambuco (ICB/UPE), Rua Arnóbio Marques, 310, Santo Amaro, Recife 50100-130, PE, Brazil
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Panjaitan NSD, Lienggonegoro LA, Nikmah UA. Response to Article "Serum Levels of Galectin-9 are Increased in Cervical Cancer Patients and are Higher in Advanced Clinical Stages" [Letter]. Onco Targets Ther 2022; 15:1417-1418. [PMID: 36457761 PMCID: PMC9707536 DOI: 10.2147/ott.s396547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 11/22/2022] [Indexed: 11/26/2022] Open
Affiliation(s)
- Novaria Sari Dewi Panjaitan
- Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong Science Center, Bogor, West Java, Indonesia,Correspondence: Novaria Sari Dewi Panjaitan, Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Genomic Building, Cibinong Science Center, Jl. Raya Bogor No. 490, Cibinong – Bogor Km. 46, Bogor, West Java, Indonesia, Email
| | - Lisa Andriani Lienggonegoro
- Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong Science Center, Bogor, West Java, Indonesia
| | - Uly Alfi Nikmah
- Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong Science Center, Bogor, West Java, Indonesia
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Niang DGM, Gaba FM, Diouf A, Hendricks J, Diallo RN, Niang MDS, Mbengue B, Dieye A. Galectin-3 as a biomarker in breast neoplasms: Mechanisms and applications in patient care. J Leukoc Biol 2022; 112:1041-1052. [PMID: 36125083 DOI: 10.1002/jlb.5mr0822-673r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 08/26/2022] [Indexed: 12/24/2022] Open
Abstract
Galectin-3 is a member of the lectin family encoded by the LGALS3 gene on chromosome 14. It is secreted by a wide range of immune cells and mammary tumor cells. Through its activity on the tumor microenvironment, in particular on tumor-infiltrating leukocytes, galectin-3 improves the proliferation, survival, and colonizing ability of mammary neoplastic cells. Consequently, galectin-3 expression in the tumor microenvironment could worsen therapeutic outcomes of breast neoplasms and become a biomarker and a therapeutic target in combined immunotherapy in breast neoplasms. There is a limited amount of information that is available on galectin-3 in breast cancer in Africa. In this review, we analyze how galectin-3 influences the tumor microenvironment and its potential as a biomarker and therapeutic target in breast neoplasms. We aim to emphasize the significance of investigating galectin-3 in breast neoplasms in Africa based on the results of studies conducted elsewhere.
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Affiliation(s)
- Doudou Georges Massar Niang
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Folly Mawulolo Gaba
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Adame Diouf
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Jacobus Hendricks
- Department of Physiology and Environmental Health, University of Limpopo, Sovenga, Limpopo province, South Africa
| | - Rokhaya Ndiaye Diallo
- Division of Human Genetics, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Maguette Deme Sylla Niang
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Babacar Mbengue
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
| | - Alioune Dieye
- Division of Immunology, School of Medicine, Pharmacy and Dentistry, Cheikh Anta Diop University, Dakar, Senegal
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Reyes-Vallejo T, Conde-Rodríguez I, Serna-Villalobos J, Ramírez-Díaz I, Pérez-Villalobos G, Delgado-López G, Vazquez-Zamora VJ, Gutiérrez-Quiroz CT, Ávila-Jiménez L, García-Carrancá A, Martínez-Acosta L, Santos-López G, Reyes-Leyva J, Vallejo-Ruiz V. Serum Levels of Galectin-9 are Increased in Cervical Cancer Patients and are Higher in Advanced Clinical Stages. Onco Targets Ther 2022; 15:1211-1220. [PMID: 36246733 PMCID: PMC9556277 DOI: 10.2147/ott.s378933] [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: 06/17/2022] [Accepted: 09/27/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Cervical cancer (CC) is the second most frequent cancer in undeveloped countries. Serum biomarkers could be useful for evaluation of the treatment response and as a complementary means to improve diagnosis. The expression of galectin-9 is altered in cancer tissue, and higher concentrations are found in the serum of cancer patients. The objectives of this study were (a) to determine the serum galectin-9 concentration in patients with intraepithelial lesions and CC, (b) to determine if the concentration was related to the clinicopathological characteristics and (c) to determine if the galectin-9 concentration was related to its expression level in tumour tissue. Patients and Methods In all, 222 serum samples from women with different diagnoses, including premalignant lesions and CC, as well as samples from women with normal cytology were included in the study. The serum galectin-9 concentration was determined by ELISA. To evaluate the expression level of galectin-9 in CC tissue, immunohistochemistry was performed in 34 CC biopsy specimens. Results The galectin-9 concentration in the serum of CC patients (8.171 ng/mL) was increased compared with serum from women with normal epithelia (4.654 ng/mL) and those with low-grade (4.806 ng/mL) and high-grade (5.354 ng/mL) intraepithelial lesions (p value < 0.0001). The area under the ROC curve considering the CC group and the control group was 0.882. The optimal cut-off value was ≥6.88 ng/mL, the specificity obtained was 100%, and the sensitivity was 68.2%. In the CC group, the analysis of the clinical stage showed an increase of galectin-9 in the advanced stage IV group. Serum galectin-9 was not related to the level of galectin-9 expression in tissue, which suggests that galectin-9 is not secreted by tumour cells. Conclusion The serum galectin-9 concentration is related to cancer progression, as the level of this protein is higher in patients with advanced-stage disease.
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Affiliation(s)
- Tania Reyes-Vallejo
- Departamento de Ciencias Químico-Biológicas, Universidad de las Américas Puebla, Puebla, México
| | - Ileana Conde-Rodríguez
- Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | | | - Ivonne Ramírez-Díaz
- Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | | | - Guadalupe Delgado-López
- Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Atlixco, Puebla, México
| | | | | | - Laura Ávila-Jiménez
- Organo de Operación Administrativa Desconcentrada Estatal Morelos, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, México
| | - Alejandro García-Carrancá
- Universidad Nacional Autónoma de México Instituto Nacional de Cancerología, Ciudad de México, México
| | | | - Gerardo Santos-López
- Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Atlixco, Puebla, México
| | - Julio Reyes-Leyva
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México
| | - Verónica Vallejo-Ruiz
- Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Atlixco, Puebla, México,Correspondence: Verónica Vallejo-Ruiz, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Federal Atlixco-Metepec, s/n, Z.C, Atlixco, Puebla, 74360, México, Tel +52 24 44 440 122, Email ;
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Yao H, Yan C, Qiumin H, Li Z, Jiao A, Xin L, Hong L. Epidemiological Trends and Attributable Risk Burden of Cervical Cancer: An Observational Study from 1990 to 2019. Int J Clin Pract 2022; 2022:3356431. [PMID: 36263235 PMCID: PMC9546700 DOI: 10.1155/2022/3356431] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 07/29/2022] [Indexed: 11/20/2022] Open
Abstract
Background Cervical cancer, especially in underdeveloped areas, poses a great threat to human health. In view of this, we stratified the age and social demographic index (SDI) based on the epidemiological development trend and attributable risk of cervical cancer in countries and regions around the world. Methods According to the data statistics of the global burden of disease database (GBD) in the past 30 years, we adopted the annual percentage change (EAPCs) to evaluate the incidence trend of cervical cancer, that is, incidence rate, mortality, and disability adjusted life expectancy (DALY). Meanwhile, we investigated the potential influence of SDI on cervical cancer's epidemiological trends and relevant risk factors for cervical cancer-related mortality. Results In terms of incidence rate and mortality, the high SDI areas were significantly lower than those of low SDI areas. The incidence and mortality in women aged 20 to 39 were relatively stable, whereas an upward trend existed in patients aged 40 to 59. The global cervical cancer incidence rate increased from 335642 in 1990 to 565541 in 2019 (an increase of 68.50%, with an average annual growth rate of 2.28%), while the age-standardized incidence rate (ASIR) showed a slight downward trend of 14.91/100000 people (95% uncertainty interval [UI], 13.37-17.55) in 1990 to 13.35/100,000 persons (95% UI, 11.37-15.03) in 2019. The number of annual deaths at a global level increased constantly and there were 184,527 (95% UI, 164,836-218,942) deaths in 1990 and 280,479 (95% UI, 238,864-313,930) deaths in 2019, with an increase of 52.00%(average annual growth rate: 1.73%). The annual age-standardized disability adjusted annual life rate showed a downward trend (decline range: 0.95%, 95% confidence interval [CI], from -1.00% to - 0.89%). In addition, smoking and unsafe sex were the main attributable hazard factors in most GBD regions. Conclusions In the past three decades, the increase in the global burden of cervical cancer is mainly concentrated in underdeveloped regions (concentrated in low SDI). On the contrary, in countries with high sustainable development index, the burden of cervical cancer tends to be reduced. Alarmingly, ASIR in areas with low SDI is on the rise, which suggests that policy makers should pay attention to the allocation of public health resources and focus on the prevention and treatment of cervical cancer in underdeveloped areas, so as to reduce its incidence rate, mortality, and prognosis.
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Affiliation(s)
- Hu Yao
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
- Department of Obstetrics and Gynecology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, China
| | - Chen Yan
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - He Qiumin
- Department of Obstetrics and Gynecology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, China
| | - Zhou Li
- Department of Obstetrics and Gynecology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, China
| | - Ai Jiao
- Department of Urinary Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, China
| | - Li Xin
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Li Hong
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
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Chen M, Shi JL, Zheng ZM, Lin Z, Li MQ, Shao J. Galectins: Important Regulators in Normal and Pathologic Pregnancies. Int J Mol Sci 2022; 23:ijms231710110. [PMID: 36077508 PMCID: PMC9456357 DOI: 10.3390/ijms231710110] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/27/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Galectins (Gal) are characterized by their affinity for galactoside structures on glycoconjugates. This relationship is mediated by carbohydrate recognition domains, which are multifunctional regulators of basic cellular biological processes with high structural similarity among family members. They participate in both innate and adaptive immune responses, as well as in reproductive immunology. Recently, the discovery that galectins are highly expressed at the maternal–fetal interface has garnerd the interest of experts in human reproduction. Galectins are involved in a variety of functions such as maternal–fetal immune tolerance, angiogenesis, trophoblast invasion and placental development and are considered to be important mediators of successful embryo implantation and during pregnancy. Dysregulation of these galectins is associated with abnormal and pathological pregnancies (e.g., preeclampsia, gestational diabetes mellitus, fetal growth restriction, preterm birth). Our work reviews the regulatory mechanisms of galectins in normal and pathological pregnancies and has implications for clinicians in the prevention, diagnosis and treatment of pregnancy-related diseases.
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Affiliation(s)
- Min Chen
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Jia-Lu Shi
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Zi-Meng Zheng
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Zhi Lin
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
| | - Ming-Qing Li
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
- NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, China
- Correspondence: (M.-Q.L.); (J.S.)
| | - Jun Shao
- Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China
- Department of Obstetrics, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011, China
- Correspondence: (M.-Q.L.); (J.S.)
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Xu HH, Wang HL, Xing TJ, Wang XQ. A Novel Prognostic Risk Model for Cervical Cancer Based on Immune Checkpoint HLA-G-Driven Differentially Expressed Genes. Front Immunol 2022; 13:851622. [PMID: 35924232 PMCID: PMC9341272 DOI: 10.3389/fimmu.2022.851622] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/31/2022] [Indexed: 12/24/2022] Open
Abstract
Human leukocyte antigen G (HLA-G) is a potential checkpoint molecule that plays a key role in cervical carcinogenesis. The purpose of this study was to construct and validate a prognostic risk model to predict the overall survival (OS) of cervical cancer patients, providing a reference for individualized clinical treatment that may lead to better clinical outcomes. HLA-G-driven differentially expressed genes (DEGs) were obtained from two cervical carcinoma cell lines, namely, SiHa and HeLa, with stable overexpression of HLA-G by RNA sequencing (RNA-seq). The biological functions of these HLA-G-driven DEGs were analysed by GO enrichment and KEGG pathway using the “clusterProfiler” package. The protein-protein interactions (PPIs) were assessed using the STRING database. The prognostic relevance of each DEG was evaluated by univariate Cox regression using the TCGA-CESC dataset. After the TCGA-CESC cohort was randomly divided into training set and testing set, and a prognostic risk model was constructed by LASSO and stepwise multivariate Cox regression analysis in training set and validated in testing set or in different types of cervical cancer set. The predictive ability of the prognostic risk model or nomogram was evaluated by a series of bioinformatics methods. A total of 1108 candidate HLA-G-driven DEGs, including 391 upregulated and 717 downregulated genes, were obtained and were enriched mostly in the ErbB pathway, steroid biosynthesis, and MAPK pathway. Then, an HLA-G-driven DEG signature consisting of the eight most important prognostic genes CD46, LGALS9, PGM1, SPRY4, CACNB3, PLIN2, MSMO1, and DAGLB was identified as a key predictor of cervical cancer. Multivariate Cox regression analysis showed that this signature is an independent risk factor for the overall survival of CESC patients. Kaplan-Meier survival analysis showed that the 5-year overall survival rate is 23.0% and 84.6% for the high-risk and low-risk patients, respectively (P<0.001). The receiver operating characteristic (ROC) curve of this prognostic model with an area under the curve (AUC) was 0.896 for 5 years, which was better than that of other clinical traits. This prognostic risk model was also successfully validated in different subtypes of cervical cancer, including the keratinizing squamous cell carcinoma, non-keratinizing squamous cell carcinoma, squamous cell neoplasms, non-squamous cell neoplasms set. Single-sample gene set enrichment (ssGSEA) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis confirmed that this signature influence tumour microenvironment and immune checkpoint blockade. A nomogram that integrated risk score, age, clinical stage, histological grade, and pathological type was then built to predict the overall survival of CESC patients and evaluated by calibration curves, AUC, concordance index (C-index) and decision curve analysis (DCA). To summarize, we developed and validated a novel prognostic risk model for cervical cancer based on HLA-G-driven DEGs, and the prognostic signature showed great ability in predicting the overall survival of patients with cervical cancer.
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Affiliation(s)
- Hui-Hui Xu
- Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province, Linhai, China
- *Correspondence: Hui-Hui Xu, ; Xue-Quan Wang,
| | - Hui-Li Wang
- Department of Burn, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China
| | - Tong-Jin Xing
- Department of Infectious Disease, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China
| | - Xue-Quan Wang
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province, Linhai, China
- Department of Radiation Oncology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, China
- *Correspondence: Hui-Hui Xu, ; Xue-Quan Wang,
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Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer. Int J Mol Sci 2022; 23:ijms23116054. [PMID: 35682732 PMCID: PMC9180969 DOI: 10.3390/ijms23116054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/23/2022] [Accepted: 05/26/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Cervical cancer is one of the most common malignancies in women in terms of prevalence and mortality. Cervical cancer has some particularities that distinguish it from any other oncologic pathology: first, it is completely preventable by prompt detection of its precursor, cervical intraepithelial neoplasia (CIN); second, the Human Papillomavirus (HPV) infection is a known etiological agent; third, the mean age at diagnosis is much lower than in other oncologic conditions, as a consequence of the sexually-transmitted HPV. Methods: We evaluated the expression level of several long noncoding RNAs and a microRNA in samples from 30 patients with CIN, 9 with cervical cancer and 38 normal samples using qRT-PCR technology. Results: We observed higher expression levels for MEG3, DAPK1, MLH1 and MALAT1 in CIN samples than in normal samples, whereas TIMP3 and SOX1 had lower expression levels. For cancer samples, DAPK1, MLH1 and MALAT1 had higher expression, and MEG3, TIMP3 and SOX1 had lower expression when compared to normal samples. In the case of CIN versus cancer samples, only MEG3 gene showed a statistically significant difference. The expression of miR-205-5p was lower in both CIN and cancer samples compared to normal samples. Conclusion: Decreased MEG3 expression could be considered an alarm signal in the transition from a premalignant cervical lesion to invasive cancer, while altered expression levels of TIMP3, SOX1, MLH1, MALAT1 and miR-205-5p could serve as early biomarkers in the diagnosis of premalignant cervical lesions. Future studies, including a larger number of patients with CIN, will be of particular importance in validating these observations.
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Shi Y, Tang D, Li X, Xie X, Ye Y, Wang L. Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy? Front Oncol 2022; 12:889034. [PMID: 35677161 PMCID: PMC9168125 DOI: 10.3389/fonc.2022.889034] [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: 03/03/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
The galectin family of proteins has high affinity with β-galactoside-containing glycans. These proteins participate in cell growth and differentiation, cell adhesion, cell signal transduction, cell apoptosis, and other cellular activities. In recent years, a large number of studies have described the expression and correlation of galectins in different tumors. Each member of the family plays a vital role in tumor growth, progression, angiogenesis, adhesion, and tumor immune escape. Studies on the roles of galectins in lymphoma have mainly involved galectin-1, -3, -7, and -9. The results suggest that galectins may become novel targets for precise tumor treatment. This article reviews current research progress regarding galectins in lymphoma and provides new ideas for exploring them as novel targets for treating lymphoma and other important medical issues.
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Affiliation(s)
- Yuanwei Shi
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Central Laboratory, Linyi People’s Hospital, Linyi, China
| | - Danting Tang
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Central Laboratory, Linyi People’s Hospital, Linyi, China
| | - Xiaoqi Li
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Central Laboratory, Linyi People’s Hospital, Linyi, China
| | - Xiaoli Xie
- Central Laboratory, Linyi People’s Hospital, Linyi, China
| | - Yufu Ye
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lijuan Wang
- Central Laboratory, Linyi People’s Hospital, Linyi, China
- Linyi Key Laboratory of Tumor Biology, Linyi, China
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16
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Shan DD, Zheng QX, Wang J, Chen Z. Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression. World J Gastroenterol 2022; 28:1641-1655. [PMID: 35581965 PMCID: PMC9048787 DOI: 10.3748/wjg.v28.i16.1641] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/09/2022] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
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Affiliation(s)
- Dan-Dan Shan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiu-Xian Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Huang Y, Zhu Q, Xue L, Zhu X, Chen Y, Wu M. Machine Learning-Assisted Ensemble Analysis for the Prediction of Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer. Front Oncol 2022; 12:817250. [PMID: 35425697 PMCID: PMC9001844 DOI: 10.3389/fonc.2022.817250] [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: 11/17/2021] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
The clinical benefit of neoadjuvant chemotherapy (NACT) before concurrent chemoradiotherapy (CCRT) vs. adjuvant chemotherapy after CCRT is debated. Non-response to platinum-based NACT is a major contributor to poor prognosis, but there is currently no reliable method for predicting the response to NACT (rNACT) in patients with locally advanced cervical cancer (LACC). In this study we developed a machine learning (ML)-assisted model to accurately predict rNACT. We retrospectively analyzed data on 636 patients diagnosed with stage IB2 to IIA2 cervical cancer at our hospital between January 1, 2010 and December 1, 2020. Five ML-assisted models were developed from candidate clinical features using 2-step estimation methods. Receiver operating characteristic curve (ROC), clinical impact curve, and decision curve analyses were performed to evaluate the robustness and clinical applicability of each model. A total of 30 candidate variables were ultimately included in the rNACT prediction model. The areas under the ROC curve of models constructed using the random forest classifier (RFC), support vector machine, eXtreme gradient boosting, artificial neural network, and decision tree ranged from 0.682 to 0.847. The RFC model had the highest predictive accuracy, which was achieved by incorporating inflammatory factors such as platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-albumin ratio, and lymphocyte-to-monocyte ratio. These results demonstrate that the ML-based prediction model developed using the RFC can be used to identify LACC patients who are likely to respond to rNACT, which can guide treatment selection and improve clinical outcomes.
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Affiliation(s)
- Yibao Huang
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingqing Zhu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liru Xue
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoran Zhu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yingying Chen
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingfu Wu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Zhao K, Ma Z, Zhang W. Comprehensive Analysis to Identify SPP1 as a Prognostic Biomarker in Cervical Cancer. Front Genet 2022; 12:732822. [PMID: 35058964 PMCID: PMC8764398 DOI: 10.3389/fgene.2021.732822] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 12/03/2021] [Indexed: 12/24/2022] Open
Abstract
Background: SPP1, secreted phosphoprotein 1, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. Previous studies have proven SPP1 overexpressed in a variety of cancers and can be identified as a prognostic factor, while no study has explored the function and carcinogenic mechanism of SPP1 in cervical cancer. Methods: We aimed to demonstrate the relationship between SPP1 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated SPP1 expression of cervical cancer in the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of SPP1 as a differentiating factor by the area under curve (AUC) score. Cox regression and logistic regression were performed to evaluate factors associated with prognosis. The SPP1-binding protein network was built by the STRING tool. Enrichment analysis by the R package clusterProfiler was used to explore potential function of SPP1. The single-sample GSEA (ssGSEA) method from the R package GSVA and TIMER database were used to investigate the association between the immune infiltration level and SPP1 expression in cervical cancer. Results: Pan-cancer data analysis showed that SPP1 expression was higher in most cancer types, including cervical cancer, and we got the same result in the GEO database. The ROC curve suggested that SPP1 could be a potential diagnostic biomarker (AUC = 0.877). High SPP1 expression was associated with poorer overall survival (OS) (P = 0.032). Further enrichment and immune infiltration analysis revealed that high SPP1 expression was correlated with regulating the infiltration level of neutrophil cells and some immune cell types, including macrophage and DC. Conclusion: SPP1 expression was higher in cervical cancer tissues than in normal cervical epithelial tissues. It was significantly associated with poor prognosis and immune cell infiltration. Thus, SPP1 may become a promising prognostic biomarker for cervical cancer patients.
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Affiliation(s)
- Kaidi Zhao
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhou Ma
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Zhang
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Sewgobind NV, Albers S, Pieters RJ. Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology. Biomolecules 2021; 11:1720. [PMID: 34827718 PMCID: PMC8615947 DOI: 10.3390/biom11111720] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/12/2021] [Accepted: 11/13/2021] [Indexed: 12/16/2022] Open
Abstract
Galectin-7 is a soluble unglycosylated lectin that is able to bind specifically to β-galactosides. It has been described to be involved in apoptosis, proliferation and differentiation, but also in cell adhesion and migration. Several disorders and diseases are discussed by covering the aforementioned biological processes. Structural features of galectin-7 are discussed as well as targeting the protein intracellularly or extracellularly. The exact molecular mechanisms that lie behind many biological processes involving galectin-7 are not known. It is therefore useful to come up with chemical probes or tools in order to obtain knowledge of the physiological processes. The objective of this review is to summarize the roles and functions of galectin-7 in the human body, providing reasons why it is necessary to design inhibitors for galectin-7, to give the reader structural insights and describe its current inhibitors.
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Affiliation(s)
| | | | - Roland J. Pieters
- Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, NL-3508 TB Utrecht, The Netherlands; (N.V.S.); (S.A.)
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Clinical Effects of Chinese Herbal Decoction Combined with Basic Chemoradiotherapy and Nursing Intervention in the Treatment of Cervical Cancer and the Effect on Serum CEA, CA125, and TNF- α Levels. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:1446864. [PMID: 34603461 PMCID: PMC8483916 DOI: 10.1155/2021/1446864] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/08/2021] [Indexed: 01/11/2023]
Abstract
Objective This study was aimed to investigate the clinical effect of Chinese herbal decoction combined with basic chemoradiotherapy and nursing intervention in the treatment of cervical cancer and the effect on serum carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and tumor necrosis factor-α (TNF-α) levels. Methods A total of 200 cervical cancer patients in our hospital from June 2015 to November 2018 were selected and randomly divided into a study group and a control group. The control group was given chemoradiotherapy and psychological nursing treatment, and the study group was given self-made Chinese herbal decoction on the basis of the control group. The clinical efficacy and serum CEA, CA125, and TNF-α levels were assessed. Results After treatment, the total effective rate of the study group was significantly higher than that of the control group. The levels of serum CEA, CA125, and TNF-α were decreased in the two groups after treatment, and the decrease in the study group was more significant than that in the control group. After treatment, CD3+ and CD4+ levels were increased compared with those before treatment, and the increase in the study group was also more obvious than that of the control group. The level of CD8+ was decreased compared with before treatment, and the decrease in the study group was more notable than that of the control group. The two-year cumulative survival rate of the study group was markedly higher than that of the control group. The quality-of-life of patients treated for 3 months, 1 year, and 2 years was dramatically improved compared to before treatment. The incidence of adverse reactions in the study group was lower than that of the control group. Conclusion The treatment of basic chemoradiotherapy and psychological nursing intervention combined with Chinese herbal decoction on cervical cancer patients can improve the clinical treatment effects, improve the patient's body immunity, reduce serum CEA, CA125, and TNF-α levels, prolong survival time, improve life quality, and reduce the incidence of adverse reactions, and it is worthy of clinical promotion.
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Wu Q, Lu S, Zhang L, Zhao L. LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration. Reprod Sci 2021; 28:3000-3009. [PMID: 34076871 DOI: 10.1007/s43032-021-00626-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 05/16/2021] [Indexed: 01/23/2023]
Abstract
Long non-coding RNAs (lncRNAs) are crucial participants in cancer development. HOXA cluster antisense RNA 2 (HOXA-AS2) plays a tumor promoter role in bladder cancer. However, the functional role of HOXA-AS2 in cervical cancer remains unclear. Our study first found that HOXA-AS2 expression was up-regulated in cervical cancer cells. Then functional analysis including cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing uncovered that reduction of HOXA-AS2 remarkably impeded cell proliferation and migration in cervical cancer. Additionally, luciferase reporter assays were performed to confirm that HOXA-AS2 activated Notch signaling pathway via the mediation of independent recombination signal binding protein for JK (RBP-JK) activity. As we know, Notch intracellular domain (NICD) is associated with RBP-JK in the nucleus to promote target genes in the Notch pathway. Through RNA immunoprecipitation (RIP), RNA pull down, and fluorescent in situ hybridization (FISH) assays, we observed that HOXA-AS2 combined with NICD. Moreover, the data from Co-IP assays indicated that HOXA-AS2 reduction weakened the interaction of NICD and RBP-JK. Collectively, HOXA-AS2 played a cancer-promoting role in cervical cancer development by modulating the Notch pathway, which might become a novel target for cervical cancer treatment.
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Affiliation(s)
- Qunxiong Wu
- Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, Ningbo, 315000, Zhejiang, China
| | - Shentao Lu
- Department of Gynecological Pelvic Floor and Oncology, Chongqing Health Center for Women and Children, Chongqing, 401120, China.
| | - Li Zhang
- Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, Ningbo, 315000, Zhejiang, China
| | - Lingjun Zhao
- Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, Ningbo, 315000, Zhejiang, China
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The Cyr61 Is a Potential Target for Rotundifuran, a Natural Labdane-Type Diterpene from Vitex trifolia L., to Trigger Apoptosis of Cervical Cancer Cells. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6677687. [PMID: 34234887 PMCID: PMC8218918 DOI: 10.1155/2021/6677687] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 04/29/2021] [Accepted: 05/08/2021] [Indexed: 12/26/2022]
Abstract
Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from Vitex trifolia L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC50 less than 10 μM), via induction of apoptosis in vitro, and the antitumor effect of RTF is further confirmed on the HeLa cell-inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species- (ROS-) induced mitochondrial-dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability- (DARTS-) combined mass spectrometry (DARTS-MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.
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23
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The complexity of tumour angiogenesis based on recently described molecules. Contemp Oncol (Pozn) 2021; 25:33-44. [PMID: 33911980 PMCID: PMC8063899 DOI: 10.5114/wo.2021.105075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 11/23/2020] [Indexed: 12/13/2022] Open
Abstract
Tumour angiogenesis is a crucial factor associated with tumour growth, progression, and metastasis. The whole process is the result of an interaction between a wide range of different molecules, influencing each other. Herein we summarize novel discoveries related to the less known angiogenic molecules such as galectins, pentraxin-3, Ral-interacting protein of 76 kDa (RLIP76), long non-coding RNAs (lncRNAs), B7-H3, and delta-like ligand-4 (DLL-4) and their role in the process of tumour angiogenesis. These molecules influence the most important molecular pathways involved in the formation of blood vessels in cancer, including the vascular endothelial growth factor (VEGF)-vascular endothelial growth factor receptor interaction (VEGFR), HIF1-a activation, or PI3K/Akt/mTOR and JAK-STAT signalling pathways. Increased expression of galectins, RLIP76, and B7H3 has been proven in several malignancies. Pentraxin-3, which appears to inhibit tumour angiogenesis, shows reduced expression in tumour tissues. Anti-angiogenic treatment based mainly on VEGF inhibition has proved to be of limited effectiveness, leading to the development of drug resistance. The newly discovered molecules are of great interest as a potential source of new anti-cancer therapies. Their role as targets for new drugs and as prognostic markers in neoplasms is discussed in this review.
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24
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Yang Y, Han A, Wang X, Yin X, Cui M, Lin Z. Lipid metabolism regulator human hydroxysteroid dehydrogenase-like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis. J Cell Mol Med 2021; 25:4846-4859. [PMID: 33738911 PMCID: PMC8107089 DOI: 10.1111/jcmm.16461] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 02/02/2021] [Accepted: 02/05/2021] [Indexed: 12/28/2022] Open
Abstract
Human hydroxysteroid dehydrogenase‐like 2 (HSDL2) is a potent regulator in cancers and is also involved in lipid metabolism, but the role of HSDL2 in cervical cancer and whether it regulates the progress of cervical cancer through lipid metabolism remains unclear. In this study, we found that the overexpression of HSDL2 was in relation with cervical cancer progression including lymph nodes metastasis and recurrence. HSDL2 could serve as a novel marker of early diagnosis in cervical cancer. HSDL2 also gave impetus to tumorigenesis by initiating and promoting proliferation, invasion and migration of cervical cancer cells (Hela, C33A and SiHa) through EMT. Interestingly, we also searched that HSDL2 participated in oncogenesis by regulating lipid metabolism. In sum, our results gave the novel insight of HSDL2 functions which could be the potential for being the biomarker of prognosis and new target of therapy.
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Affiliation(s)
- Yang Yang
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
| | - Anna Han
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
| | - Xinyue Wang
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
| | - Xianglin Yin
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
| | - Minghua Cui
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
| | - Zhenhua Lin
- Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.,Key Laboratory of the Science and Technology Department of Jilin Province, Yanji, China
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25
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HOXD-AS1 facilitates cell migration and invasion as an oncogenic lncRNA by competitively binding to miR-877-3p and upregulating FGF2 in human cervical cancer. BMC Cancer 2020; 20:924. [PMID: 32977766 PMCID: PMC7519495 DOI: 10.1186/s12885-020-07441-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/21/2020] [Indexed: 01/01/2023] Open
Abstract
Background Long non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression. Previous studies have identified the oncogenic lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in human cancers, while its roles in cervical cancer (CC) remain unclear. Herein we intended to characterize the implication of HOXD-AS1 in CC. Methods qRT-PCR was applied to examine the relative expression of HOXD-AS1 in CC tissues, cell lines and transfected cells. Wound healing and transwell assays were applied to detect cell migration and invasion alteration. The targeting relationship between miRNA and mRNA/lncRNA was determined by dual luciferase reporter, qRT-PCR and western blot assays. Results HOXD-AS1 was overexpressed in CC tissues and cell lines. Its higher level predicted worse prognosis of CC patients. SiRNA mediated knockdown of HOXD-AS1 repressed CC cell migration and invasion, and its overexpression did the opposite. Mechanistically, HOXD-AS1 acted as a competing endogenous RNA (ceRNA) to sponge miR-877-3p and led to upregulation of FGF2, a target of miR-877-3p. Importantly, either miR-877-3p overexpression or FGF2 inhibition could abolish the migration and invasion promotion induced by HOXD-AS1. Conclusion HOXD-AS1 functions as a tumor-promoting lncRNA via the miR-877-3p/FGF2 axis in CC. HOXD-AS1 might be a promising therapeutic target as well as a novel prognostic biomarker for CC.
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26
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Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases. Biomolecules 2020; 10:biom10030389. [PMID: 32138174 PMCID: PMC7175224 DOI: 10.3390/biom10030389] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 02/28/2020] [Accepted: 03/01/2020] [Indexed: 12/11/2022] Open
Abstract
Galectin-3 is a β-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.
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27
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Neuropilin: Handyman and Power Broker in the Tumor Microenvironment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1223:31-67. [PMID: 32030684 DOI: 10.1007/978-3-030-35582-1_3] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Neuropilin-1 and neuropilin-2 form a small family of transmembrane receptors, which, due to the lack of a cytosolic protein kinase domain, act primarily as co-receptors for various ligands. Performing at the molecular level both the executive and organizing functions of a handyman as well as of a power broker, they are instrumental in controlling the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. In this setting, the various neuropilin ligands and interaction partners on various cells of the tumor microenvironment, such as cancer cells, endothelial cells, cancer-associated fibroblasts, and immune cells, are surveyed. The suitability of various neuropilin-targeting substances and the intervention in neuropilin-mediated interactions is considered as a possible building block of tumor therapy.
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28
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Chetry M, Song Y, Pan C, Li R, Zhang J, Zhu X. Effects of Galectin-1 on Biological Behavior in Cervical Cancer. J Cancer 2020; 11:1584-1595. [PMID: 32047564 PMCID: PMC6995396 DOI: 10.7150/jca.38538] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 11/22/2019] [Indexed: 02/06/2023] Open
Abstract
Background: We previously revealed that the expression of galectin-1 (LGALS1) was significantly reduced after neoadjuvant chemotherapy treatment in cervical cancer patients. The objective of this study is to investigate the effects of LGALS1 expression on biological behaviors of cervical cancer cells. Methods: Immunohistochemistry and immunocytochemistry were performed to detect the expression of LGALS1 in cervical cancer tissues and cells (SiHa and C33A). Western blot analysis was performed to evaluate the efficacy of lentivirus-mediated upregulation or downregulation of LGALS1 in cervical cancer cells. Cell viability and proliferation were detected by CCK-8 and BrdU assays, respectively. Annexin V-FITC/PI apoptosis detection kit was employed to measure the apoptosis of cervical cancer cells. Transwell invasion and migration assays were also conducted to explore the invasive and migratory capabilities of cervical cancer cells. The expression of apoptosis- (Bcl-2 and Bax), invasion- (MMP-2 and MMP-9), and migration-related (Fascin and Ezrin) proteins, were detected by Western blot analysis. Xenograft mouse model of cervical cancer was generated to explore whether LGALS1 overexpression could promote tumor growth in vivo. Results: LGALS1 was overexpressed in cervical cancer tissues and cell lines compared to that in normal cervical tissues and epithelium cells. Upregulation of LGALS1 significantly promoted the cell proliferation, inhibited cell apoptosis, and enhanced the migratory and invasive abilities of both SiHa and C33A cells, whereas downregulation of LGALS1 led to the opposite results. The level of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin expression was significantly upregulated in cervical cancer cells with LGALS1 overexpression, while converse results were obtained in LGALS1 knockdown cancer cells. In vivo study also showed that LGALS1 overexpression facilitated tumor growth of cervical cancer cells. Conclusion: Overexpression of LGALS1 significantly promoted and enhanced the aggressive features of cervical cancer both in vitro and in vivo, which may be associated with high expression of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin proteins.
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Affiliation(s)
| | | | | | | | | | - Xueqiong Zhu
- Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
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29
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Qiu HZ, Huang J, Xiang CC, Li R, Zuo ED, Zhang Y, Shan L, Cheng X. Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis. Technol Cancer Res Treat 2020; 19:1533033820980112. [PMID: 33302814 PMCID: PMC7734488 DOI: 10.1177/1533033820980112] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 10/09/2020] [Accepted: 11/04/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. METHODS Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. RESULTS We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. CONCLUSIONS The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.
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Affiliation(s)
- Hui-Zhu Qiu
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Ji Huang
- Department of Pharmacy, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Cheng-Cheng Xiang
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Rong Li
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Er-Dong Zuo
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Yuan Zhang
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Li Shan
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
| | - Xu Cheng
- Department of Hematology and Oncology, Soochow University Affiliated Taicang Hospital (The First People’s Hospital of Taicang), Jiangsu, China
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Shen L, Li Y, Hu G, Huang Y, Song X, Yu S, Xu X. MIR155HG Knockdown Inhibited the Progression of Cervical Cancer by Binding SRSF1. Onco Targets Ther 2020; 13:12043-12054. [PMID: 33262605 PMCID: PMC7695692 DOI: 10.2147/ott.s267594] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 09/16/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND As the fourth most common cancer among women worldwide, cervical cancer lead to 311,000 deaths in 2018. Although the treatments have been developed, the survival rate of cervical cancer remains unsatisfactory. In this study, we aimed to identify differentially expressed lncRNAs (DEIncRNAs) between cervical cancer and adjacent normal tissues using bioinformatics analysis, and further to investigate the biological function of the DEIncRNAs in vitro and in vivo. METHODS The expression profiles from two microarray datasets (GSE6791 and GSE63514) were downloaded from GEO for analysis of DEIncRNAs between cervical cancer and adjacent normal cervical tissues. Among all DEIncRNAs, MIR155HG upregulation was identified and selected for further investigation. The effect of MIR155HG knockdown on proliferation, apoptosis and invasion in SiHa and Hela cells were evaluated. In addition, Western blot, RNA immunoprecipitation (RIP) and cell cycle assays were performed to determine the binding target of MIR155HG. Furthermore, the effect of MIR155HG knockdown on tumor growth in vivo was investigated. RESULTS The level of MIR155HG was found to be significantly upregulated in cervical cancer tissue compared with adjacent cervical tissue. Knockdown of MIR155HG notably inhibited the proliferation of SiHa and Hela cells by inducing apoptosis. In addition, MIR155HG knockdown decreased cell invasion. Moreover, tumor growth in xenograft was significantly inhibited by MIR155HG knockdown in vivo. Additionally, SRSF1 was identified as the binding protein of MIR155HG. CONCLUSION Our findings demonstrated that MIR155HG knockdown inhibited the progression of cervical cancer by binding SRSF1, inspiring the usage of MIR155HG as a potential novel therapy target for the treatment of cervical cancer.
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Affiliation(s)
- Ling Shen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong515041, People’s Republic of China
| | - Yuancheng Li
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong515041, People’s Republic of China
| | - Guiying Hu
- Department of Gynecology, Maternal and Children Hospital of Guangdong Province, Guangzhou, Guangdong511400, People’s Republic of China
| | - Yihong Huang
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong515041, People’s Republic of China
| | - Xinli Song
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Shun Yu
- Department of Gynecological Oncology, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Xiaoyuan Xu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong515041, People’s Republic of China
- Correspondence: Xiaoyuan Xu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong515041, People’s Republic of China Email
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Cervical Cancer Cells Express Markers Associated with Immunosurveillance. J Immunol Res 2019; 2019:1242979. [PMID: 31198791 PMCID: PMC6526527 DOI: 10.1155/2019/1242979] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 11/03/2018] [Accepted: 03/18/2019] [Indexed: 12/20/2022] Open
Abstract
Cervical cancer is the second most frequent cancer in women in Mexico, and its development depends on the presence of human papillomaviruses in the uterine cervix. These oncogenic viruses transform cells where the control over cell cycle disappears, and the capacity to induce apoptosis is absent. On the other hand, some mutations confer to the transformed cells the ability to evade recognition by the immune system. The expression of markers of the immune system such as CD95, MICA/B, CD39, CD73, NKp30, NKp46, CD44, CD24, NKG2A, and CTLA-4 was analysed by flow cytometry on cervical cancer cells INBL (HPV 18, stage IVB), HeLa (HPV 18), CaSki (HPV 16), and C33A (HPV-). Our results showed the presence of atypical markers on cervical cancer cells; some of them are molecules involved in tumour cell recognition such as MICA/B and CD95. Other markers associated with immune system escape, such as CD39, CD73, and CTLA-4, were also present. Furthermore, we found that some cervical cancer cells expressed typical markers of NK cells like NKp30, NKp46, NKG2A, and KIR3DL1. It is not clear whether these molecules confer any gain to the tumour cells or if they represent a disadvantage, but we hypothesise that these molecules that are present in cervical cancer cells allow them to mimic in front of the immune system.
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Niland S, Eble JA. Neuropilins in the Context of Tumor Vasculature. Int J Mol Sci 2019; 20:ijms20030639. [PMID: 30717262 PMCID: PMC6387129 DOI: 10.3390/ijms20030639] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 01/23/2019] [Accepted: 01/29/2019] [Indexed: 01/09/2023] Open
Abstract
Neuropilin-1 and Neuropilin-2 form a small family of plasma membrane spanning receptors originally identified by the binding of semaphorin and vascular endothelial growth factor. Having no cytosolic protein kinase domain, they function predominantly as co-receptors of other receptors for various ligands. As such, they critically modulate the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. This review highlights the diverse neuropilin ligands and interacting partners on endothelial cells, which are relevant in the context of the tumor vasculature and the tumor microenvironment. In addition to tumor cells, the latter contains cancer-associated fibroblasts, immune cells, and endothelial cells. Based on the prevalent neuropilin-mediated interactions, the suitability of various neuropilin-targeted substances for influencing tumor angiogenesis as a possible building block of a tumor therapy is discussed.
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Affiliation(s)
- Stephan Niland
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany.
| | - Johannes A Eble
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany.
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