title: miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin.
abstract: Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motility and resistance to anoikis and chemotherapy. HBx-dependent induction of microRNA-7, -107, and -21 was further demonstrated to directly target maspin mRNA, leading to its protein downregulation. Higher expressions of these microRNAs also correlated with maspin downregulation in HBV-associated patients, and were associated with their poor overall survival. These data not only provided new insights into the molecular mechanisms of maspin deficiency by HBx, but also indicated that downregulation of maspin by microRNAs confers HBx-mediated aggressiveness and chemoresistance in HCC.
authors: Department of Pharmacology, National Taiwan University, Taipei, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors: Wen-Shu
authors: WS
authors: Chen
authors: Internal Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors: Chia-Jui
authors: CJ
authors: Yen
authors: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.|Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.
authors: Yun-Ju
authors: YJ
authors: Chen
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan.
authors: Jhen-Yu
authors: JY
authors: Chen
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors: Li-Yun
authors: LY
authors: Wang
authors: Department of Life Sciences, Tzu Chi University, Hualien, Taiwan.|Institute of Radiation Sciences, Tzu Chi Technology College, Hualien, Taiwan.
authors: Shu-Jun
authors: SJ
authors: Chiu
authors: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors: Wen-Ling
authors: WL
authors: Shih
authors: Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.
authors: Chien-Yi
authors: CY
authors: Ho
authors: Department of Pharmacology, National Taiwan University, Taipei, Taiwan.
authors: Tzu-Tang
authors: TT
authors: Wei
authors: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.
authors: Hsiao-Lin
authors: HL
authors: Pan
authors: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.
authors: Pei-Hsuan
authors: PH
authors: Chien
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Mien-Chie
authors: MC
authors: Hung
authors: Department of Pharmacology, National Taiwan University, Taipei, Taiwan.
authors: Ching-Chow
authors: CC
authors: Chen
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors: Wei-Chien
authors: WC
authors: Huang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D023102:Anoikis / Q000187:drug effects / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D015999:Multivariate Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D035683:MicroRNAs; D015843:Serpins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C549045:MIRN107 microRNA, human; C524940:MIRN21 microRNA, human; C549242:MIRN7-1 microRNA, human; C085344:SERPIN-B5; C057628:hepatitis B virus X protein
keywords: HBx; hepatocellular carcinoma cell; maspin; metastasis; microRNA