title: Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-alpha-induced apoptosis.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have emerged as novel genetic regulators of cell functions such as proliferation, apoptosis and cancer.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the role of a specific miRNA in modulating hepatic cell functions.
  
  
  METHODS
  C57Bl/6 mice were administered anti-fas receptor antibodies to induce liver cell apoptosis. miRNAs were purified from the liver tissue and evaluated using an miRNA microarray. The role of miRNA-491_5p, which was overexpressed in the model, in modulating hepatic cell functions was evaluated. miRNA-491_5p was overexpressed in Hep G2 cells, followed by the addition of tumour necrosis factor (TNF)-alpha, and induction of apoptosis as well as genes involved in apoptosis pathways were evaluated. The effect of miRNA-491_5p target genes on apoptosis was also analysed by inhibiting their expression by siRNA-induced gene silencing.
  
  
  RESULTS
  Upregulation of miRNA-491_5p was found in a high-dose anti-fas receptor antibody group. Overexpression of microRNA-491_5p sensitized Hep G2 cells for TNF-alpha-induced apoptosis, and also caused an inhibition of alpha-fetoprotein, (AFP), heat shock protein-90 (hsp-90) and nuclear factor-kappaB (NF-kappaB). Overexpression of miRNA-491_5p or inhibition of AFP and hsp-90 resulted in an increased apoptosis in TNF-alpha-treated Hep G2 cells.
  
  
  CONCLUSIONS
  One of the miRNAs that is associated with the acute liver injury mouse model, miRNA-491_5p, sensitizes Hep G2 cells for TNF-alpha-induced apoptosis, at least in part, by inhibiting AFP, hsp-90 and NF-kappaB.
authors.affiliation: Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Sangjeong
authors.initials: S
authors.lastname: Yoon
authors.forename: Tae-Hun
authors.initials: TH
authors.lastname: Kim
authors.forename: Arutselvan
authors.initials: A
authors.lastname: Natarajan
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Wang
authors.forename: Jeongwoo
authors.initials: J
authors.lastname: Choi
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zern
authors.forename: Senthil K
authors.initials: SK
authors.lastname: Venugopal
mesh_terms: D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D019014:fas Receptor / Q000276:immunology
chemical_list: D000906:Antibodies; C551675:MIRN491 microRNA, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor