MiR‐17~92 ablation impairs liver regeneration in an estrogen‐dependent manner
| Autor: | Hong Bu, Lei Zhang, Yongjie Zhou, Yujun Shi, Li Li, Jie Xia, Fei Chen, Hongjie Ji, Xu-Feng Lu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male 0301 basic medicine medicine.medical_specialty Ovariectomy Early Regeneration Mice 03 medical and health sciences Sex Factors Internal medicine medicine Animals Hepatectomy PTEN liver regeneration Carbon Tetrachloride Cell Proliferation Mice Knockout Regulation of gene expression Oncogene biology miR‐17˜92 Cell growth Regeneration (biology) PTEN Phosphohydrolase Estrogens Original Articles Cell Biology Liver regeneration Cell biology MicroRNAs 030104 developmental biology Endocrinology Gene Expression Regulation Liver Hepatocytes biology.protein Molecular Medicine Female Original Article gender disparity Chemical and Drug Induced Liver Injury Signal transduction oestrogen Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.12782 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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