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

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.