MicroRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and inhibits the migration of human hepatocellular carcinoma HepG2 cells

• Published in: International journal of molecular medicine Vol. 34; no. 2; pp. 420 - 428
• Main Authors: LIU, WEIWEI, XU, CHUANMING, WAN, HUIFANG, LIU, CHUNJU, WEN, CAN, LU, HONGFEI, WAN, FUSHENG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-08-2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Apoptosis; Apoptosis - genetics; Breast cancer; Cancer therapies; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell cycle; cell cycle arrest; Cell Cycle Checkpoints - genetics; Cell growth; Cell Movement - genetics; Development and progression; Gene expression; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genetic aspects; Health aspects; Hep G2 Cells; hepatocellular carcinoma; Hepatoma; Humans; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Lung cancer; Medical prognosis; Metastasis; MicroRNA; microRNA-206; MicroRNAs - biosynthesis; migration; Mortality; Neoplasm Proteins - biosynthesis; Properties; Rodents; Studies; tumor suppressor; Tumors
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2014.1800

MicroRNA-206 (miR-206) is known to regulate cell proliferation and migration and is involved in various types of cancer. However, the role of miR-206 in human hepatocellular carcinoma (HHC) has not been previously reported. In the present study, the expression of Notch3 in HCC and adjacent non-neoplastic tissue was immunohistochemically assessed on formalin-fixed, paraffin-embedded sections. miR-206 mimics were transiently transfected into HepG2 cells using Lipofectamine™ 2000. Subsequently, we evaluated the role of miR-206 in cell proliferation, apoptosis, cell cycle arrest and migration by MTS assay, Hoechst 33342 staining, Annexin V-FITC/PI assay, flow cytometry and wound healing assay. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis, we detected the expression of Notch3, Bax, Bcl-2, Hes1, p57 and matrix metalloproteinase (MMP)-9 at the mRNA and protein level, respectively. In addition, we measured the expression of miR-206 at the mRNA level and that of caspase-3 at the protein level. After miR-206 was upregulated in HepG2 cells, Notch3, Hes1, Bcl-2 and MMP-9 were downregulated both at the mRNA and protein level, whereas p57 and Bax were upregulated. Cleaved caspase-3 protein expression was also markedly increased. Cell proliferation was significantly attenuated and apoptosis was markedly increased. Furthermore, miR-206 overexpression induced cell cycle arrest and inhibited the migration of HepG2 cells. Taken together, our results uggest that miR-206 is a potential regulator of apoptosis, the cell cycle and migration in HepG2 cells and that it has the potential for use in the targeted therapy of HCC and is a novel tumor suppressor.