MicroRNA-148b Acts as a Tumor Suppressor in Cervical Cancer by Inducing G1/S-Phase Cell Cycle Arrest and Apoptosis in a Caspase-3-Dependent Manner
Zongmei Mou, Xiangting Xu, Mei Dong, Jin Xu
Department of Gynaecology, People’s Hospital of Rizhao, Rizhao, Shandong, China (mainland)
Med Sci Monit 2016; 22:2809-2815
Available online: 2016-08-09
The purpose of our study was to investigate the role of microRNA (miR)-148b in cervical cancer.
MATERIAL AND METHODS: The expression of miR-148b was determined in HPV-16-immortalized cervical epithelial cell line CRL-2614 cells and in cervical cancer cell line HeLa cells. The miR-148b mimics or scrambled RNA were then transfected into Hela cells. Forty-eight hours after transfection, the mRNA expression of miR-148b and DNA methyltransferase 1 (DNMT1) were confirmed. Cell proliferation ability (cell viability and colony formation ability), invasion ability, and apoptosis were assessed after transfection with miR-148b mimics or scrambled RNA, as well as the protein expression of cyclin D1 and caspase-3.
RESULTS: The expression of miR-148b was significantly downregulated in HeLa cells compared with CRL2614 cells (P<0.05), but was statistically upregulated by transfection with miR-148b mimics compared with the cells transfected with scrambled RNA (P<0.05). Also, we found that the expression of DNMT1 was significantly decreased by transfection with miR-148b mimics (P<0.05). Additionally, miR-148b mimics significantly decreased the cell proliferation ability and invasion ability, and statistically induced apoptosis. Furthermore, the expression of cyclin D1 protein was significantly decreased and the expression of caspase-3 protein was significantly increased by miR-148b mimics compared with that in the cells transfected with scrambled RNA (P<0.05).
CONCLUSIONS: Our results suggest that overexpression of miR-148b protects against cervical cancer by inducing G1/S-phase cell cycle arrest and apoptosis through caspase-3-dependent manner, and overexpression of miR-148b might develop a therapeutic intervention for cervical cancer.
Keywords: Cell Cycle Checkpoints - genetics, Caspase 3 - metabolism, Apoptosis - genetics, Cell Line, Tumor, Cell Survival - genetics, Down-Regulation, G1 Phase Cell Cycle Checkpoints - genetics, Hela Cells, MicroRNAs - metabolism, Transfection, Uterine Cervical Neoplasms - pathology