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.

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