title: miR-222 overexpression may contribute to liver fibrosis in biliary atresia by targeting PPP2R2A.
abstract: OBJECTIVE
  Biliary atresia (BA) is a devastating liver disease in infants. Progressive hepatic fibrosis is often observed in postoperative patients with BA even after a successful Kasai portoenterostomy procedure. MicroRNA-222 (miRNA) has been linked to the activation of stellate cells and the progression of liver fibrosis.
  
  
  METHODS
  In this study, the miR-222 expression profile in BA and infants with anicteric choledochal cyst (CC) was determined. The functional effect of miR-222 inhibition on the growth of the human hepatic stellate cell line LX-2 was also evaluated. The downstream signaling pathways and target of miR-222 were determined by coupling gene expression profiling and pathway analysis and by in silico prediction, respectively. In addition, we demonstrated miR-222 overexpression in patients with BA compared with choledochal cyst controls.
  
  
  RESULTS
  Inhibition of miR-222 in the LX-2 cell line significantly decreased cell proliferation. We also identified protein phosphatase 2A subunit B as a target of miR-222. The downstream signaling pathway, Akt, was also influenced by miR-222. A consistent reduction of Akt phosphorylation and Ki67 in the LX-2 line was shown following miR-222 suppression.
  
  
  CONCLUSIONS
  Our results show that miR-222 overexpression is common in BA and contributes to LX-2 cell proliferation by targeting protein phosphatase 2A subunit B and Akt signaling.
authors.affiliation: *Department of Pediatric Surgery, Children's Hospital, Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health †Department of Immunology, Shanghai Medical College, Fudan University, and Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.forename: Yijie
authors.initials: Y
authors.lastname: Zheng
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhou
authors.forename: Shan
authors.initials: S
authors.lastname: Zheng
mesh_terms: D001656:Biliary Atresia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002460:Cell Line; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D011171:Portoenterostomy, Hepatic; D011446:Prospective Studies; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D054648:Protein Phosphatase 2; D051057:Proto-Oncogene Proteins c-akt; C525710:MIR222, human; C512974:PPP2R2A protein, human; C494918:AKT1 protein, human