title: Down-regulation of microRNA-26a promotes mouse hepatocyte proliferation during liver regeneration.
abstract: BACKGROUND
  Inadequate liver regeneration (LR) is still an unsolved problem in major liver resection and small-for-size syndrome post-living donor liver transplantation. A number of microRNAs have been shown to play important roles in cell proliferation. Herein, we investigated the role of miR-26a as a pivotal regulator of hepatocyte proliferation in LR.
  
  
  RESULTS
  Adult male C57BL/6J mice, undergoing 70% partial hepatectomy (PH), were treated with Ad5-anti-miR-26a-LUC or Ad5-miR-26a-LUC or Ad5-LUC vector via portal vein. The animals were subjected to in vivo bioluminescence imaging. Serum and liver samples were collected to test liver function, calculate liver-to-body weight ratio (LBWR), document hepatocyte proliferation (Ki-67 staining), and investigate potential targeted gene expression of miR-26a by quantitative real-time PCR and Western blot. The miR-26a level declined during LR after 70% PH. Down-regulation of miR-26a by anti-miR-26a expression led to enhanced proliferation of hepatocytes, and both LBWR and hepatocyte proliferation (Ki-67(+) cells %) showed an increased tendency, while liver damage, indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (T-Bil), was reduced. Furthermore, CCND2 and CCNE2, as possible targeted genes of miR-26a, were up-regulated. In addition, miR-26a over-expression showed converse results.
  
  
  CONCLUSIONS
  MiR-26a plays crucial role in regulating the proliferative phase of LR, probably by repressing expressions of cell cycle proteins CCND2 and CCNE2. The current study reveals a novel miRNA-mediated regulation pattern during the proliferative phase of LR.
authors.affiliation: Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Ju
authors.forename: Dongping
authors.initials: D
authors.lastname: Wang
authors.forename: Linwei
authors.initials: L
authors.lastname: Wu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C486196:Ccnd2 protein, mouse; C503689:Ccne2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D012333:RNA, Messenger