Human hepatocellular carcinoma cell growth is suppressed by all-trans-retinoicacid through down-regulating miR-18a expression

Abstract

Objective To investigate the inhibitory effect of all-tram-retinoicacid (ATRA) on HCC cell growth and probe the potential molecular mechanism.Methods HCC cell lines,HepG2 and SMMC-7721 were treated by ATRA and cell growth was analyzed by using MTT assay.The expression levels of miR-18a were evaluated in HepG2 and SMMC-7721,compared with the normal livers pool by using RealTime PCR analysis.Cell growth analysis by using MTT assay was performed on HepG2 and SMMC-7721 after transfection with anti-miR-18a.Rescued assay was designed to probe the mechanism of ATRA on cell growth by using ATRA with or without miR-18a mimic.Results HepG2 cell growth was suppressed about 74％ (P＜0.05,36 h),72％ (P＜0.01,48 h),and 67％ (P＜0.05,72 h) and SMMC-7721 cell growth was inhibited about 68％ (P＜0.05,48 h),and 64％ (P＜0.05,72 h) after treatment with ATRA,compared with the cells treated with Ethanol.MiR-18a expression was up-regulated in HepG2 and SMMC-7721 cell lines about 4.7- and 3.8-fold (P＜0.05),respectively.Endogenous miR-18a levels were down-regulated by ATRA about 67％ and 56％ (P＜0.05).The inhibitory effect of ATRA on HCC cell growth was reversed about 1.2-fold (P＜0.05,48 h) by overexpression of miR-18a in HepG2 cells and cell growth of SMMC-7721 was enhanced about 1.25- and 1.2-fold (P＜0.05,24 and 48 h) with ectopic expression of miR-18a.Conclusion HCC cells growth is suppressed by ATRA through miR-18a mediated network. Key words: ATRA; Hepatocellular carcinoma; miR-18a; Cell growth