title: MicroRNA-147 suppresses human hepatocellular carcinoma proliferation migration and chemosensitivity by inhibiting HOXC6.
abstract: 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 HCCin vitroproliferation and migration, increased 5-FU chemosensitivity, and reducedin vivotumorigenicity. 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 inhibitedin vitroproliferation and migration, and increased 5-FU chemosensitivity in HCC. On the other hand, HOXC6 overexpression reversed the inhibitory effect of miR-147 on HCCin vitroproliferation. Therefore, our results suggest that miR-147 can modulates HCC development through the regulation on HOXC6.
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Sui
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Shen
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Dai
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Jiong-Jiong
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Min-Feng
authors.initials: MF
authors.lastname: Zhang
authors.affiliation: Department of Special Medical Care and Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai 200438, China.
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Yang
keywords: HOXC6; chemosensitivity; hepatocellular carcinoma; miR-147; migration; proliferation