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microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma.
- Source :
-
International journal of oncology [Int J Oncol] 2014 Jun; Vol. 44 (6), pp. 2085-92. Date of Electronic Publication: 2014 Mar 19. - Publication Year :
- 2014
-
Abstract
- Our recent study of the microRNA (miRNA) expression signature of hypopharyngeal squamous cell carcinoma (HSCC) revealed that microRNA-504 (miR-504) is significantly downregulated in HSCC tissues, suggesting that this miRNA is a candidate tumor suppressor. However, several previous reports indicated that miR-504 has an oncogenic function through targeting TP53. The aim of this study was to investigate the functional significance of miR-504 in cancer cells and to identify novel targets regulated by this miRNA in HSCC cells. First, we confirmed the downregulation of miR-504 in HSCC clinical specimens (P<0.0001) by qPCR. Using two sources of miR-504 to restore function, we observed significant inhibition of cancer cell proliferation in head and neck SCC (HNSCC) cell lines (FaDu, SAS and HSC3) and HCT116 colon carcinoma cells (p53+/+ and p53-/-). In HNSCC cells, induction of cell cycle arrest was observed by miR-504 transfection. To identify the molecular targets of miR-504, we performed gene expression analysis of miR-504 transfectants and in silico database analyses. Our data showed that cell cycle-related genes (RB1, CDK6, CDC23 and CCND1) were candidate target genes of miR-504. In HSCC clinical specimens, the expression of cyclin-dependent kinase 6 (CDK6) was significantly higher in cancer tissues compared to non-cancer tissues (P=0.0004). A significant inverse correlation between CDK6 and miR-504 expression was found (r=-0.43, P=0.0039). Expression of miR-504 inhibited CDK6 expression in HNSCC cells. Loss of tumor-suppressive miR-504 enhanced HSCC cell proliferation through targeting CDK6. The identification of novel tumor-suppressive miR-504-mediated molecular pathways and targets provide new insights into HSCC oncogenesis.
- Subjects :
- Carcinoma, Squamous Cell genetics
Cell Line, Tumor
Cell Proliferation
Databases, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms genetics
Humans
Hypopharyngeal Neoplasms genetics
Male
MicroRNAs genetics
Squamous Cell Carcinoma of Head and Neck
Transfection
Carcinoma, Squamous Cell pathology
Cyclin-Dependent Kinase 6 genetics
Cyclin-Dependent Kinase 6 metabolism
Head and Neck Neoplasms pathology
Hypopharyngeal Neoplasms pathology
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 44
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24647829
- Full Text :
- https://doi.org/10.3892/ijo.2014.2349