title: MicroRNA-34a regulates liver regeneration and the development of liver cancer in rats by targeting Notch signaling pathway.
abstract: OBJECTIVE
  This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway.
  
  
  METHODS
  Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. Dual-luciferase reporter gene assay was performed to examine whether miR-34a targeted Notch1 gene. Human liver cancer Huh7 cells were transfected and divided into blank, negative control (NC), miR-34a mimics and miR-34a inhibitors groups. MTT and flow cytometry were used to detect cell growth, and cell cycle and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miR-34a and Notch receptor mRNA. Western blotting was performed to detect the protein expressions of Notch receptors, P21, Bax, Bcl-2 and Bcl-xL. Tumor xenograft in nude mice was done to observe tumor formation in different groups.
  
  
  RESULTS
  Compared to the SH group, miR-34a expression in liver tissues in the PH group decreased first and then increased to the normal level during LR. In early stage of LR, the expressions of Notch receptors and miR-34a were negatively correlated. Compared to the blank and NC groups, the cell growth was inhibited, cell cycle was mainly arrested in the G2/M phase and cell apoptosis rate increased in the miR-34a mimics group. Moreover, the expressions of miR-34a, P21 and Bax were up-regulated, while the expressions of Notch receptors, and Bcl-2 and Bcl-xL were down-regulated in this group. Additionally, the tumor growth in the miR-34a mimics group was reduced. The miR-34a inhibitors group showed contrary tendencies.
  
  
  CONCLUSIONS
  Our study demonstrates that miR-34a regulated LR and the development of liver cancer by inhibiting Notch signaling pathway.
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Chuan-Bao
authors.initials: CB
authors.lastname: Chen
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Zheng
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Xiao-Shun
authors.initials: XS
authors.lastname: He
authors.affiliation: Third Division of Organ Transplant Center, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P. R. China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014183:Transplantation, Heterologous
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C522425:MIRN34 microRNA, human; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1
keywords: Notch signaling pathway; liver cancer; liver regeneration; microRNA-34a