title: miR-382 targeting PTEN-Akt axis promotes liver regeneration.
abstract: Liver regeneration is a highly orchestrated process which can be regulated by microRNAs (miRNAs, miRs), though the mechanisms are largely unclear. This study was aimed to identify miRNAs responsible for hepatocyte proliferation during liver regeneration. Here we detected a marked elevation of miR-382 in the mouse liver at 48 hrs after partial hepatectomy (PH-48h) using microarray analysis and qRT-PCRs. miR-382 overexpression accelerated the proliferation and the G1 to S phase transition of the cell cycle both in mouse NCTC1469 and human HL7702 normal liver cells, while miR-382 downregulation had inverse effects. Moreover, miR-382 negatively regulated PTEN expression and increased Akt phosphorylation both in vitro and in vivo. Using PTEN siRNA and Akt activator/inhibitor, we further found that PTEN inhibition and Akt phosphorylation were essential for mediating the promotive effect of miR-382 in the proliferation and cell growth of hepatocytes. Collectively, our findings identify miR-382 as a promoter for hepatocyte proliferation and cell growth via targeting PTEN-Akt axis which might be a novel therapeutic target to enhance liver regeneration capability.
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Department of Experimental Biochemistry and Physiology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, Skopje, Republic of Macedonia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Dimitrova-Shumkovska
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, Nanjing University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D020536:Enzyme Activators / Q000494:pharmacology; D006498:Hepatectomy; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D023421:Models, Animal; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D020536:Enzyme Activators; C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C000612266:microRNA 382, mouse; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse
keywords: Akt; PTEN; liver regeneration; microRNA; proliferation