title: LncRNA-ATB/microRNA-200a/β-catenin regulatory axis involved in the progression of HCV-related hepatic fibrosis.
abstract: OBJECTIVE
  Long noncoding RNAs (lncRNAs)-activated by transforming growth factor beta (lncRNA-ATB) is known to be involved in the invasion of hepatocellular carcinoma by regulating target genes of miR-200a. However, the role and molecular mechanisms of lncRNA-ATB/miR-200a in HCV-related liver fibrosis remains unclear. In this study, we examined the expression of lncRNA-ATB/miR-200a, and their target gene β-Catenin in liver tissues of HCV patients and hepatic stellate cells (HSCs) to elucidate the possible role of lncRNA-ATB/miR-200a axis in HSC activation and development of liver fibrosis.
  
  
  METHODS
  Liver tissues were obtained by biopsy or surgery from eighteen HCV patients with severe liver fibrosis and six healthy subjects (control). Conditioned media (CM) from cultured HepG2-CORE cells (HepG2 cells stably expressing HCV core protein) were used to treat LX-2 cells. The binding sites between lncRNA-ATB/miR-200a and β-catenin were predicted and then verified by a dual luciferase reporter assay. The effect of lncRNA-ATB/miR-200a/β-catenin on HSC activation was assessed by examining the expression of alpha-smooth muscle actin (α-SMA) and collagen type 1 alpha 1 (Col1A1) in HSCs. Further, the regulatory role of lncRNA-ATB on HSC activation and miR-200a/β-catenin expression was assessed by using siRNA-mediated knockdown of lncRNA-ATB.
  
  
  RESULTS
  LncRNA-ATB was up-regulated in fibrotic liver tissues and activated LX-2 cells treated with CM from HepG2-CORE cells. Dual luciferase reporter assays confirmed that lncRNA-ATB contained common binding sites for miR-200a and β-catenin. Decreased expression of miR-200a and increased expression of β-catenin were observed in liver tissues of patients with HCV-related hepatic fibrosis and activated HSCs. Knockdown of lncRNA-ATB could down-regulate β-catenin expression by up-regulating the endogenous miR-200a and suppress the activation of LX-2 cells.
  
  
  CONCLUSIONS
  LncRNA-ATB/miR-200a/β-catenin regulatory axis likely contributed to the development of liver fibrosis in HCV patients. Knockdown of lncRNA-ATB might be a novel therapeutic target for HCV-related liver fibrosis.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Na
authors.initials: N
authors.lastname: Fu
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Su-Xian
authors.initials: SX
authors.lastname: Zhao
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Kong
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Du
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Ren
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Zhang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Wen-Cong
authors.initials: WC
authors.lastname: Li
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Po
authors.initials: P
authors.lastname: Cui
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Rong-Qi
authors.initials: RQ
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China.
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 050051 Shijiazhuang, China. Electronic address: nanyuemin@163.com.
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Nan
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000302:isolation & purification; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051176:beta Catenin; C000619854:long non-coding RNA ATB, human; D003094:Collagen
keywords: Hepatic stellate cells; Liver fibrosis; Long noncoding RNA; Long noncoding RNA-activated by transforming growth factor beta; microRNA-200a; β-Catenin