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
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
Externí odkaz: