title: Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT.
abstract: The mutant of virus is a frequent event. Hepatitis B virus X protein (HBx) plays a vital role in the development of hepatocellular carcinoma (HCC). Therefore, the identification of potent mutant of HBx in hepatocarcinogenesis is significant. Previously, we identified a natural mutant of the HBx gene (termed HBxΔ127). Relative to wild type HBx, HBxΔ127 strongly enhanced cell proliferation and migration in HCC. In this study, we aim to explore the mechanism of HBxΔ127 in promotion of proliferation of hepatoma cells. Our data showed that both wild type HBx and HBxΔ127 could increase the expression of miR-215 in hepatoma HepG2 and H7402 cells. However, HBxΔ127 was able to significantly increase miR-215 expression relative to wild type HBx in the cells. We identified that protein tyrosine phosphatase, receptor type T (PTPRT) was one of the target genes of miR-215 through targeting 3'UTR of PTPRT mRNA. In function, miR-215 was able to promote the proliferation of hepatoma cells. Meanwhile anti-miR-215 could partially abolish the enhancement of cell proliferation mediated by HBxΔ127 in vitro. Knockdown of PTPRT by siRNA could distinctly suppress the decrease of cell proliferation mediated by anti-miR-215 in HepG2-XΔ127/H7402-XΔ127 cells. Moreover, we found that anti-miR-215 remarkably inhibited the tumor growth of hepatoma cells in nude mice. Collectively, relative to wild type HBx, HBxΔ127 strongly enhances proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Our finding provides new insights into the mechanism of HBx mutant HBxΔ127 in promotion of proliferation of hepatoma cells.
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China; Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Fabao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: You
authors.affiliation: Department of Hepatology, The First Hospital, Jilin University, Changchun 130021, PR China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Hepatology, The First Hospital, Jilin University, Changchun 130021, PR China. Electronic address: junqiniu@yahoo.com.cn.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: zhangxd@nankai.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D034622:RNA Interference; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D020121:5' Untranslated Regions; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; D050505:Mutant Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C516865:PTPRT protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: HBx mutant; HCC; Hepatitis B virus X protein; PTPRT; Proliferation; miR-215