MicroRNA-147 suppresses human hepatocellular carcinoma proliferation migration and chemosensitivity by inhibiting...

Patients with hepatocellular carcinoma (HCC) experience poor prognosis and low survival rates. In this study, we explored the molecular mechanism of microRNA-147 (miR-147) in regulating human HCC. We firstly used quantitative RT-PCR (qRT-PCR) to compare the expression levels of miR-147 between 7 HCC and two normal liver cell lines, as well as 10 paired primary HCC tissues and their adjacent non-carcinoma tissues. We found miR-147 was down-regulated in both HCC cell lines and primary HCCs tissues. HCC cell lines HepG2 and HuH7 were transfected with lentiviral vector of miR-147 mimics. We found overexpressing miR-147 significantly inhibited HCC in vitro proliferation and migration, increased 5-FU chemosensitivity, and reduced in vivo tumorigenicity. Luciferase, qRT-PCR and western blot assays showed that HOXC6 was the downstream target of miR-147, and both gene and protein levels of HOXC6 were down-regulated by miR-147 in HCC cells. SiRNA mediated HOXC6 knockdown inhibited in vitro proliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCC in vitro proliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.