miR-378 suppresses HBV-related hepatocellular carcinoma tumor growth by directly targeting the insulin-like growth factor 1 receptor / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the impact and mechanism of microRNA (miR)-378 on hepatocellular carcinoma (HCC) cell growth.</p><p><b>METHODS</b>The human hepatoma cell line HepG2 and its derivative HepG2.2.15 (stably expressing hepatitis B virus (HBV)) were transduced with lentiviruses expressing miR-378 or non-expressing controls (nc-Lv). Effects on cell proliferation were assessed by the MTT assay and on colony-formation efficiency by clonogenic assay. Targets of miR-378 were predicted by bioinformatic analysis and validated by luciferase reporter assay in the human embryonic kidney cell line HEK293. Real-time polymerase chain reaction and western blotting were used to monitor expression of the endogenous targets in miR-378- overexpressing HepG2 and HepG2.2.15 cells.</p><p><b>RESULTS</b>The HepG2 and HepG2.2.15 cells transduced with lentivirus expressing miR-378 showed significantly lower cell proliferation and colony formation than the control cells transduced with nc-Lv (P less than 0.01 and P less than 0.05, respectively). The insulin-like growth factor 1 receptor (IGF1R) was predicted as a potential target of miR-378, and luciferase reporter activity of IGF1R was significantly decreased in the HEK293 cells co-transfected with miR-378 (by 41.8% vs. the control cells, P less than 0.01). Moreover, the miRNA-378-mediated effect was narrowed down to the 3'-untranslated region (UTR) of IGF1R. The miRNA-378-mediated reduction of IGF1R specifically involved its protein expression (P less than 0.01) and not its mRNA expression (P more than 0.05).</p><p><b>CONCLUSION</b>miR-378 may suppress growth characteristics of HBV-related HCC by directly targeting the IGF1R 3'-UTR and inhibiting its protein expression.</p>