title: MiR-19a regulates PTEN expression to mediate glycogen synthesis in hepatocytes.
abstract: MiR-19a, a member of mir-17-92 microRNA clusters, has been demonstrated to promote cell proliferation and angiogenesis via regulating the PI3K/AKT pathway, the major insulin signaling pathway. However, whether miR-19a plays an important role in glycogen synthesis in hepatocytes remains unknown. Here, we define the impact of miR-19a on glycogen synthesis and IL-6-induced reduced glycogenesis in hepatocytes and its underlying mechanisms. Our studies indicate that miR-19a was down-regulated in the livers of db/db mice and mice injected with IL-6, as well as mouse NCTC 1469 hepatocytes and HEP 1-6 hepatocytes treated by IL-6. We found that over-expression of miR-19a in NCTC 1469 cells and HEP 1-6 cells led to increased activation of the AKT/GSK pathway and synthesis of glycogen, whereas down-regulation of miR-19a impaired AKT/GSK phosphorylation and glycogenesis. Over-expression of miR-19a ameliorated IL-6-induced reduced glycogen synthesis in hepatocytes. Moreover, we identified PTEN as the target of miR-19a by a luciferase assay. Down-regulation of PTEN rescued the effects of miR-19a suppression on the activation of the AKT/GSK pathway and improved glycogenesis in NTC 1469 cells. These findings show for the first time that miR-19a might activate the AKT/GSK pathway and glycogenesis via down-regulation of PTEN expression.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.affiliation: 1] Peking University Fifth School of Clinical Medicine, Beijing, China [2] Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.affiliation: First Affiliated Hospital of Jiamusi University, Jiamusi, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sui
authors.affiliation: 1] Peking University Fifth School of Clinical Medicine, Beijing, China [2] Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xi
authors.affiliation: 1] Peking University Fifth School of Clinical Medicine, Beijing, China [2] Key Laboratory of Geriatrics, Beijing Institute of Geriatrics &Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006003:Glycogen / Q000096:biosynthesis*; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015850:Interleukin-6; C561642:MIRN19 microRNA, mouse; D035683:MicroRNAs; D006003:Glycogen; D019869:Phosphatidylinositol 3-Kinases; D038341:Glycogen Synthase Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse