MicroRNA-199a-5p inhibits VEGF-induced tumorigenesis through targeting oxidored-nitro domain-containing protein 1 in human HepG2 cells.

VEGF induces deterioration of hepatocellular carcinoma (HCC) by enhancing cell proliferation and migration. MicroRNAs regulate many cellular processes. In this study, we examined the regulation of tumorigenesis in HCC cells by microRNAs in relation to the effect of VEGF. Differences in microRNA expression between HepG2 and THLE-3 cells were characterized by microarray analysis. The results showed that miR-199a-5p expression was markedly downregulated in HepG2 cells and was inhibited in VEGF-overexpressing HepG2 cells in a dose- and time-dependent manner. This miRNA also inhibited cell proliferation and migration, as demonstrated by MTT and cell migration assays. Oxidored-nitro domain-containing protein 1 (NOR1), a nitroreductase, was identified as a downstream target gene of miR-199a-5p, and upregulation of NOR1 proved critical for the inhibition of VEGF-induced cell proliferation and migration in HepG2 cells by miR-199a-5p. These results indicate that miR-199a-5p is critical for regulating cell proliferation and migration by targeting and upregulating NOR1 in human HepG2 cells.