title: MicroRNA-34c targets TGFB-induced factor homeobox 2, represses cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma.
abstract: MicroRNAs (miRs) are short, non-coding RNAs with post-transcriptional regulatory functions. Previous studies have demonstrated that miR-34c is involved in diverse biological processes, including carcinogenesis. The aim of the present study was to investigate the role of miR-34c and its target genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Expression levels of miR-34c and its predicted target genes were measured. The target genes were validated by a luciferase assay. The effects of miR-34c restoration were evaluated by the detection of HBV antigens, cell proliferation and apoptosisin vitro, in addition to the tumor growthin vivo. The data demonstrated that miR-34c was downregulated in HBV-associated HCC clinical tissues and HCC cell lines compared with their corresponding controls. transforming growth factor-β-induced factor homeobox 2 (TGIF2), a transcription factor repressing transforming growth factor-β (TGFβ) signaling, was observed to be upregulated and was identified as a target gene of miR-34c. The restoration of miR-34c in HepG2.2.15 cells suppressed TGIF2 expression, HBV replication and viral antigen synthesis; inhibited cell proliferation; and induced apoptosis. miR-34c also inhibited tumor growth in a mouse model. The present study indicates that miR-34c may act as a tumor suppressor by targeting TGIF2 during HBV-associated hepatocellular carcinogenesis. miR-34c and TGIF2 may represent key regulatory factors, diagnostic markers and therapeutic targets for the prevention and treatment of HBV-associated HCC.
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neurobiology Institute, Jining Medical University, Jining, Shandong 272067, P.R. China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.affiliation: Emergency Department, Chinese Frontier Defence Armed Police General Hospital, Shenzhen, Guangdong 510080, P.R. China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China ; Shandong Quality Inspection Center for Medical Devices, Jinan, Shandong 250012, P.R. China.
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Fan
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, inan, Shandong 250012, P.R. China ; Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Rui-Feng
authors.initials: RF
authors.lastname: Li
authors.affiliation: Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Zhen-Hai
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Liu
keywords: TGFB-induced factor homeobox 2; hepatitis B virus; hepatocellular carcinoma; microRNA; microRNA-34c