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

Med Sci Monit. 2016 Aug 9:22:2809-15. doi: 10.12659/msm.896862.

Abstract

BACKGROUND 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.

MeSH terms

  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • Genes, Tumor Suppressor*
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN148 microRNA, human
  • MicroRNAs
  • Caspase 3