MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6

MicroRNAs serve a critical role in human hepatocellular carcinoma (HCC) progression. However, the exact role of microRNA-143 (miR-143) in HCC remains unclear. The current study investigates the molecular mechanism of miR-143 in HCC. In cultured HepG2 and Bel7402 cell lines, miR-143 levels were raised by lentivirus transduction. This significantly inhibited HCC progression in terms of cell invasion and proliferation in both HepG2 and Bel7402 cell lines (P<0.05). MiR-143 also significantly decreased tumor implantation in vivo (P<0.05). Regulation of miR-143 on its direct target, GATA-binding factor 6 (GATA6), was investigated by multiple strategies, including dual-luciferase assay, quantitative polymerase chain reaction and western blot analysis. The results indicated that miR-143 was downregulated in both HCC cell lines and human tumors. GATA6 was identified as the downstream target of miR-143 in HCC, and overexpressing GATA6 was able to counter the tumor-suppressive effect of miR-143 on HCC in HepG2 and Bel7402 cells by significantly increasing proliferation and invasion rates (P<0.05). Therefore, a novel epigenetic pathway was identified in which miR-143 may suppress the malignancy of HCC by targeting GATA6.