title: LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p.
abstract: OBJECTIVE
  It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear.
  
  
  METHODS
  Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined.
  
  
  RESULTS
  LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p.
  
  
  CONCLUSIONS
  We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
authors.affiliation: Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D053630:Depsides
chemical_list: D001572:Benzofurans; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051176:beta Catenin; C543614:Mirn17 microRNA, mouse; C076944:salvianolic acid B; D053630:Depsides
keywords: Hepatic stellate cells; LincRNA-p21; Salvianolic acid B; Wnt/β-catenin pathway; microRNA-17-5p