Overexpression of miR-125a-5p Inhibits Hepatocyte Proliferation through the STAT3 Regulation In Vivo and In Vitro

被引:5
|
作者
Zhang, Chunyan [1 ,2 ,3 ,4 ,5 ,6 ]
Zhao, Yabin [1 ,4 ]
Wang, Qiwen [1 ,2 ,3 ,4 ,5 ,6 ]
Qin, Jianru [1 ,4 ]
Ye, Bingyu [1 ,2 ,3 ,4 ,5 ,6 ]
Xu, Cunshuan [1 ,4 ]
Yu, Guoying [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Henan Normal Univ, State Key Lab Cell Differentiat & Regulat, Xinxiang 453007, Henan, Peoples R China
[2] Henan Normal Univ, Henan Int Joint Lab Pulm Fibrosis, Xinxiang 453007, Henan, Peoples R China
[3] Henan Normal Univ, Henan Ctr Outstanding Overseas Scientists Pulm Fi, Xinxiang 453007, Henan, Peoples R China
[4] Henan Normal Univ, Coll Life Sci, Xinxiang 453007, Henan, Peoples R China
[5] Henan Normal Univ, Inst Biomed Sci, Xinxiang 453007, Henan, Peoples R China
[6] Henan Normal Univ, Overseas Expertise Intro Ctr Discipline Innovat P, Xinxiang 453007, Henan, Peoples R China
关键词
miR-125a; STAT3; proliferation; liver regeneration; cell cycle; CANCER STEM-CELLS; LIVER-REGENERATION; HEPATOCELLULAR-CARCINOMA; RAT-LIVER; MICRORNA-21; PATHWAY; EXPRESSION; STRATEGIES; PHASE;
D O I
10.3390/ijms23158661
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
microRNAs (miRNAs) are critically involved in liver regeneration (LR). miR-125a-5p (miR-125a) is a tumor-suppressing miRNA, but its role in LR has not been studied. Our previous studies have proved that miR-125a was related to LR at the initiation phase, while the mechanism hepatocyte proliferation triggered by miR-125a in LR has been rarely evaluated. Herein, we mainly studied the molecular mechanism of miR-125a in triggering hepatocyte proliferation and the proliferation stage of LR. Firstly, a striking reduction of miR-125a was found at 24 h as well as 30 h following partial hepatectomy (PH) in rat liver tissue by miRNAs expression profiles as well as qRT-PCR analysis. Furthermore, in vitro, upregulation of miR-125a decreased proliferation as well as G(1)/S conversion, which promoted hepatocytes apoptosis. STAT3 was the target of miR-125a. In vivo, upregulation of miR-125a by tail vein injection of agomir inhibited LR index. Upregulation of miR-125a inhibited LR index and hepatocytes proliferation by STAT3/p-STAT3/JUN/BCL2 axis. In summary, these current discoveries indicated that miR-125a inhibited hepatocytes proliferation as well as LR by targeting STAT3 and via acting on the STAT3/p-STAT3/JUN/BCL2 axis.
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页数:15
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