title: MicroRNA-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.
abstract: Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.|The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Pang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.|The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D008112:Liver Glycogen; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C532375:Mirn20 microRNA, mouse; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase
keywords: PTEN; glycogen synthesis; miR-20a-5p; p53; p63