MiR-27a promotes hepatocellular carcinoma cell proliferation through suppression of its target gene peroxisome proliferator-activated receptor γ.
- Author:
Shuo LI
;
Jing LI
;
Bing-Yuan FEI
;
Dan SHAO
;
Yue PAN
;
Zhan-Hao MO
;
Bao-Zhen SUN
;
Dan ZHANG
;
Xiao ZHENG
;
Ming ZHANG
;
Xue-Wen ZHANG
1
;
Li CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Carcinoma, Hepatocellular; genetics; metabolism; Cell Proliferation; genetics; physiology; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; genetics; metabolism; MicroRNAs; genetics; physiology; PPAR gamma; metabolism
- From: Chinese Medical Journal 2015;128(7):941-947
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDMicroRNAs (miRNAs) function as essential posttranscriptional modulators of gene expression, and are involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs are deregulated in hepatocellular carcinoma (HCC). This study aimed to investigate the role of miR-27a in the development of HCC.
METHODSThe expression of MiR-27a was measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to examine changes in the viability of HepG2, Bel-7402, Bel-7404 hepatoma cell lines associated with up-regulation or down-regulation of miR-27a. A dual-luciferase activity assay was used to verify a target gene of miR-27a. Immunohistochemistry, qRT-PCR, Western blotting analysis, and cell cycle and apoptosis flow cytometric assays were used to elucidate the mechanism by which miR-27a modulates liver cancer cell proliferation.
RESULTSThe expression of miR-27a was significantly increased in HCC tissues and HepG2, Bel-7402, Bel-7404 hepatoma cell lines (P < 0.05). We also found that the down-regulation of miR-27a in HepG2 cells dramatically inhibited proliferation, blocked the G1 to S cell cycle transition and induced apoptosis (P < 0.05). In addition, miR-27a directly targeted the 3'- untranslated region of peroxisome proliferator-activated receptor γ (PPAR-γ), and ectopic miR-27a expression suppressed PPAR-γ expression on the mRNA and protein levels. The rosiglitazone-induced overexpression of PPAR-γ attenuated the effect of miR-27a in HCC cells.
CONCLUSIONSOur findings suggested that miRNA-27a promoted HCC cell proliferation by regulating PPAR-γ expression. MiR-27a may provide a potential therapeutic strategy for HCC treatment.