title: Analysis of microRNA expression profile induced by AICAR in mouse hepatocytes.
abstract: AMP-activated protein kinase (AMPK) has been proposed to act as a key energy sensor mediating the metabolism of glucose and lipids, and pharmacological activation of AMPK may provide a new strategy for the management of type 2 diabetes. MicroRNAs (miRNAs) are a group of endogenous noncoding RNA that play important roles in many biological processes including energy metabolism. Whether miRNAs mediate AMPK action in regulating metabolic process is not clear. In this study, 0.5mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) was added to increase activation of AMPK in 8 week old C57BL/6 mice primary hepatocytes. MiRNA microarray was performed to compare the miRNA expression profiles of hepatocytes treated with or without AICAR. We discovered that 41 miRNAs were significantly altered in AICAR-treated sample (fold change: >2) compared with untreated control sample. Among them, 19 miRNAs were upregulated. MiRNA targets were predicted by TargetScan. Further bioinformatic analysis indicated that these predicted targets might be mainly involved in pathways of cellular metabolism and tumor pathogenesis. FUNDO analysis suggested that these predicted targets were enriched in cancer, diabetes mellitus, hypertension, obesity and heart failure (P<0.01). A series of miRNAs could be regulated by the activation of AMPK and might mediate the action of AMPK during metabolic processes and tumor pathogenesis. Predicted target genes discovered in this study and pathway analysis provide new insights into hepatic metabolism and tumor pathogenesis regulated by AMPK signaling and clues to the possible molecular mechanism underlying the effect of AMPK.
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D012265:Ribonucleotides / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D007004:Hypoglycemic Agents; D035683:MicroRNAs; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide