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Upregulated microRNA-199a-5p inhibits nuclear receptor corepressor 1 translation in mice with non‑alcoholic steatohepatitis.

Abstract
Mounting evidence indicates that dysregulated microRNAs (miRNAs) are important in the etiology and pathogenesis of steatohepatitis. However, the functions of miRNAs in the pathophysiological process of non-alcoholic steatohepatitis (NASH) are poorly understood. In this study, C57BL/6J mice were fed a methionine-choline‑deficient (MCD) diet for eight weeks in order to induce hepatic steatohepatitis. Using reverse transcription polymerase chain reaction, the hepatic expression levels of miR-199a-5p, miR-122 and miR-221 in the mice were examined. Bioinformatic analysis of dysregulated miR-199a-5p was performed to predict the potential role of miR‑199a‑5p in NASH. The MCD diet was found to significantly reduce miR-122 expression levels and significantly increase miR‑199a-5p expression levels in mouse livers, compared with those of mice fed a control diet. In the bioinformatic analysis, miR‑199a‑5p was identified to be predominantly involved in transcription, protein serine/threonine kinase activity, insulin signaling, and the Wnt and mitogen‑activated protein kinase signaling pathways. The regulation of nuclear receptor corepressor 1 (NCOR1) by miR‑199a-5p was also examined by silencing and overexpressing this miRNA in LX-2 cells. The data revealed that NCOR1 protein levels were significantly reduced and enhanced by miR-199a-5p mimic and inhibitor, respectively. These findings suggest a key role for miR-199a-5p in the progression of NASH through inhibition of NCOR1 translation, and provide novel insights into NASH pathogenesis.
AuthorsBinggui Zhang, Rongqi Wang, Jinghua Du, Jingya Niu, Rui Zhang, Shunjiang Xu, Xuemin Niu, Qingfu Zhang, Yuemin Nan
JournalMolecular medicine reports (Mol Med Rep) Vol. 10 Issue 6 Pg. 3080-6 (Dec 2014) ISSN: 1791-3004 [Electronic] Greece
PMID25269746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Insulin
  • MicroRNAs
  • Mirn199 microRNA, mouse
  • Ncor1 protein, mouse
  • Nuclear Receptor Co-Repressor 1
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Cell Proliferation (genetics)
  • Computational Biology (methods)
  • Insulin (genetics)
  • Liver (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs (genetics)
  • Mitogen-Activated Protein Kinases (genetics)
  • Non-alcoholic Fatty Liver Disease (genetics)
  • Nuclear Receptor Co-Repressor 1 (genetics)
  • Protein Biosynthesis (genetics)
  • Protein-Serine-Threonine Kinases (genetics)
  • Signal Transduction (genetics)
  • Transcriptional Activation (genetics)
  • Up-Regulation (genetics)
  • Wnt Signaling Pathway (genetics)

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