miR-382 targeting PTEN-Akt axis promotes liver regeneration

// Yihua Bei 1,* , Yang Song 2,* , Fei Wang 2 , Jasmina Dimitrova-Shumkovska 1,3 , Yang Xiang 4 , Yingying Zhao 2 , Jingqi Liu 2 , Junjie Xiao 1,5 and Changqing Yang 2 1 Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China 2 Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China 3 Department of Experimental Biochemistry and Physiology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, Skopje, Republic of Macedonia 4 State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, Nanjing University, Nanjing, China 5 Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Changqing Yang, email: // Junjie Xiao, email: // Keywords : microRNA, liver regeneration, proliferation, PTEN, Akt Received : August 18, 2015 Accepted : November 16, 2015 Published : December 01, 2015 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.