MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN
MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN
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MicroRNA-21 通过靶向 PTEN 促进肝脏再生
DOI：
10.12659/msm.896157
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发表时间：
2016-01-08
影响因子：
3.1
通讯作者：
Yang, Changqing
中科院分区：
文献类型：
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作者：
Chen, Xiaoyu;Song, Meiyi;Yang, Changqing
研究背景包括miR-21在内的多种microRNA（miRNAs，miRs）已被证实是肝再生的关键调节因子，但其在肝细胞增殖和细胞周期进程中的作用机制仍远未阐明。材料/方法在70%部分肝切除术后48 h（PH-48 h），使用qRT-PCR测定小鼠肝脏中的miR-21水平。通过使用细胞计数试剂盒-8（CCK-8）、EdU掺入染色和流式细胞术来测定细胞增殖。使用qRT-PCR和Western印迹分析测定磷酸酶和张力蛋白同源物（PTEN）表达。使用PTEN siRNA进行拯救实验。结果70%肝部分切除术后48 h（PH-48 h）小鼠肝脏中miR-21表达较PH后0 h（PH-0 h）显著上调。miR-21的过表达与体外BNL CL. 2正常肝细胞增殖增加和细胞周期的快速G1至S期转变相关。此外，我们发现BNL CL. 2细胞中PTEN表达与miR-21呈负相关，并证明在PH-48 h小鼠肝脏中PTEN表达较低。此外，PTEN siRNA的存在显著消除了miR-21抑制剂对肝细胞增殖的抑制作用。结论miR-21过表达可通过靶向PTEN促进肝再生和肝细胞增殖。上调miR-21可能是促进肝再生的有用治疗策略。
Background Multiple microRNAs (miRNAs, miRs), including miR-21, have been documented to be critical regulators of liver regeneration, but the mechanism underlying their roles in hepatocyte proliferation and cell cycle progression is still far from understood. Material/Methods miR-21 levels were determined using qRT-PCRs in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h). Cell proliferation was determined by use of a cell-counting kit-8 (CCK-8), EdU incorporation staining, and flow cytometry. Phosphatase and tensin homolog (PTEN) expressions were determined using qRT-PCR and Western blot analysis. PTEN siRNA was used to perform the rescue experiment. Results A marked upregulation of miR-21 was observed in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h) compared to 0 h after PH (PH-0 h). Overexpression of miR-21 was associated with increased proliferation and a rapid G1-to-S phase transition of the cell cycle in BNL CL.2 normal liver cells in vitro. In addition, we showed that PTEN expression was inversely correlated with miR-21 in BNL CL.2 cells and demonstrated that PTEN expression is lower in mouse livers at PH-48 h. Moreover, the presence of PTEN siRNA significantly abolished the suppressive effect of miR-21 inhibitor on hepatocyte proliferation. Conclusions miR-21 overexpression contributes to liver regeneration and hepatocyte proliferation by targeting PTEN. Upregulation of miR-21 might be a useful therapeutic strategy to promote liver regeneration.