title: Deep sequencing of small RNA repertoires in mice reveals metabolic disorders-associated hepatic miRNAs.
abstract: Obesity and associated metabolic disorders contribute importantly to the metabolic syndrome. On the other hand, microRNAs (miRNAs) are a class of small non-coding RNAs that repress target gene expression by inducing mRNA degradation and/or translation repression. Dysregulation of specific miRNAs in obesity may influence energy metabolism and cause insulin resistance, which leads to dyslipidemia, steatosis hepatis and type 2 diabetes. In the present study, we comprehensively analyzed and validated dysregulated miRNAs in ob/ob mouse liver, as well as miRNA groups based on miRNA gene cluster and gene family by using deep sequencing miRNA datasets. We found that over 13.8% of the total analyzed miRNAs were dysregulated, of which 37 miRNA species showed significantly differential expression. Further RT-qPCR analysis in some selected miRNAs validated the similar expression patterns observed in deep sequencing. Interestingly, we found that miRNA gene cluster and family always showed consistent dysregulation patterns in ob/ob mouse liver, although they had various enrichment levels. Functional enrichment analysis revealed the versatile physiological roles (over six signal pathways and five human diseases) of these miRNAs. Biological studies indicated that overexpression of miR-126 or inhibition of miR-24 in AML-12 cells attenuated free fatty acids-induced fat accumulation. Taken together, our data strongly suggest that obesity and metabolic disturbance are tightly associated with functional miRNAs. We also identified hepatic miRNA candidates serving as potential biomarkers for the diagnose of the metabolic syndrome.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, China.
authors.forename: Tingming
authors.initials: T
authors.lastname: Liang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D005230:Fatty Acids, Nonesterified; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse