MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway
Autor: | Heqiang Zhou, Xiaoyong Wei, Wenzheng Luo, Zhengyu Zhou, Xiaolong You, Wen Chen |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
microRNA-495 Medicine (miscellaneous) Biology Biochemistry Genetics and Molecular Biology (miscellaneous) lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Homeobox C6 Invasion Cancer stem cell Cell Movement Transforming Growth Factor beta Cell Line Tumor microRNA Gene silencing Humans lcsh:QD415-436 Epithelial–mesenchymal transition TGF-β signaling pathway Migration Cell Proliferation Homeodomain Proteins lcsh:R5-920 Cancer stem cells Squamous Cell Carcinoma of Head and Neck Research Genes Homeobox Cell Biology Cell cycle Epithelial-mesenchymal transition Gene Expression Regulation Neoplastic stomatognathic diseases MicroRNAs 030104 developmental biology Oral squamous cell carcinoma Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Carcinoma Squamous Cell Neoplastic Stem Cells Molecular Medicine Mouth Neoplasms Signal transduction Stem cell lcsh:Medicine (General) Signal Transduction |
Zdroj: | Stem Cell Research & Therapy Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-14 (2020) |
ISSN: | 1757-6512 |
Popis: | Background Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. Methods After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain- and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. Results HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. Conclusion These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway. |
Databáze: | OpenAIRE |
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