Differential Expression Of MicroRNAs In Mouse Liver Under Aberrant Energy Metabolic Status

Background/Aims:MicroRNAs (miRNAs) are a class of recently discovered,endogenous non-coding small RNAs,which play important roles in regulation of organdevelopment and differentiation,cell proliferation and apoptosis,carcinogenesis,immune response,etc.miRNAs are also demonstrated to be involved in regulation ofenergy metabolism,but only a few studies about the correlation between miRNA andhepatic energy metabolism have been reported.Although a widely accepted"two-hit"hypothesis may partially explain the progressive liver damage by non-alcoholicsteatosis and steatohepatitis,much of the pathogenesis of NAFLD remains undiscoveredMethods:The expression of microRNAs in livers of 10 ob/ob mice,8streptozotocin -induced type 1 diabetic mice and 8 normal C57BL/6 mice were analyzedby microRNA microarrays and analyzed by Significance Analysis of Microarrays.Theresults of miRNA microarrays were validated by quantitative RT-PCR.Putative targetsof the differentially-expressed miRNAs were predicted by bioinformatics algorithms formiRNA target prediction.Results:Compared to normal C57BL/6 mice,ob/ob mice showed up-regulation of8 microRNAs (miR-34a,miR-31,miR-103,miR-107,miR-194,miR-335-5p,miR-221, and miR-200a) and down-regulation of 4 microRNAs (miR-29c,miR-451,miR-21,andmiR-122) in fatty livers.Up-regulation of miR-34a and down-regulation of miR- 122was found in livers of streptozotocin-induced diabetic mice.Comparison betweenmicroRNA expressions in livers of ob/ob mice and streptozotocin-administered micefurther revealed up-regulation of 4 microRNAs (miR-103,miR-31,miR-107,andmiR-126-3p) and down-regulation of 2 microRNAs (miR-100 and miR-29c) in livers ofob/ob mice.A distinctive microRNA expression pattern was identified in ob/ob mouseliver and hierarchical clustering of this pattern could clearly discriminate ob/ob micefrom either normal C57BL/6 mice or streptozotocin-administered mice.Bybioinformatics analysis of putative miRNA targets for the differentially-expressedmiRNAs,a list of target genes were predicted,most of which are relevant to the glucoseor lipid metabolism in liver and may play important roles in NAFLDConclusion:The present study demonstrates that distinct microRNAs are stronglydysregulated in non-alcoholic fatty liver disease and hyperglycemia,suggests animportant role of microRNAs in hepatic energy metabolism and implicates theparticipation of microRNAs in the pathophysiological processes of non-alcoholic fattyliver disease.These results broadened our biological understandings of NAFLD,andoffered useful clues for future clinical applications of miRNAs as potential targets.