MiR-17~92 ablation impairs liver regeneration in an estrogen-dependent manner

Journal of Cellular and Molecular Medicine
Yongjie ZhouYujun Shi

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-...Continue Reading

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Citations

Oct 1, 2016·Scientific Reports·Rui-Ping SunYong-Liang Zhang
Apr 25, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ekaterina KachayloBostjan Humar
Aug 28, 2018·Journal of Cellular Physiology·Gui-Ling RenXiao-Ming Meng
May 25, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xia LinDong Xiao
Apr 14, 2021·Cellular and Molecular Gastroenterology and Hepatology·Xiaoyue CaoHong Bu

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Methods Mentioned

BETA
PCR
Immunoprecipitation
Assay

Software Mentioned

ImageJ
PicTar
Targetscan
SPSS

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