title: MiR-17~92 ablation impairs liver regeneration in an estrogen-dependent manner.
abstract: As one of the most important post-transcriptional regulators, microRNAs (miRNAs) participate in diverse biological processes, including the regulation of cell proliferation. MiR-17~92 has been found to act as an oncogene, and it is closely associated with cell proliferation. However, its role in liver regeneration is still unclear. We generated a hepatocyte-specific miR-17~92-deficient mouse and used a mouse model with 70% partial hepatectomy (PH) or intraperitoneal injection of carbon tetrachloride to demonstrate the role of MiR-17~92 in liver regeneration. In quiescent livers, the expression of the miR-17~92 cluster showed a gender disparity, with much higher expression in female mice. The expression of four members of this cluster was found to be markedly reduced after 70% PH. The ablation of miR-17~92 led to obvious regeneration impairment during the early-stage regeneration in the female mice. Ovariectomy greatly reduced miR-17~92 expression but significantly promoted liver regeneration in wild-type mice. In addition, early regeneration impairment in miR-17~92-deficient livers could be largely restored following ovariectomy. The proliferation suppressors p21 and Pten were found to be the target effectors of miR-17~92. MiR-17~92 disruption resulted in elevated protein levels of p21 and Pten in regenerating livers. MiR-17~92 functions as a proliferation stimulator and acts in an oestrogen-dependent manner. The loss of this miRNA results in increases in p21 and Pten expression and therefore impairs liver regeneration in female mice.
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Ji
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xia
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.|Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.affiliation: Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Chengdu, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010052:Ovariectomy; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004967:Estrogens; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D002251:Carbon Tetrachloride; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: gender disparity; liver regeneration; miR-17˜92; oestrogen