lncRNA PVT1 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting the miR-187-3p/AGO1 axis.

Jiachen Zhan, Pengfei Hu, Yujie Wang

Molecular and cellular probes 2020 Feb

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To investigate the effect of long non-coding (lnc) RNA PVT1 on apoptosis induced by doxorubicin-induced cardiotoxicity. We analyzed the expression levels of lncRNA PVT1, miR-187-3p, using reverse transcription real-time quantitative PCR (RT-qPCR) in doxorubicin-treated cardiomyocytes. The mechanism of lncRNA PVT1 in cardiotoxicity was investigated using cell transfection, CCK-8, flow cytometry, Western blot, and dual-luciferase reporter assays. Doxorubicin promotes H9c2 apoptosis and increased PVT1 expression in cardiomyocytes. Knockdown of PVT1 attenuated doxorubicin-induced cardiomyocyte apoptosis. We found that miR-187-3p is a direct target of PVT1, and that lncRNA PVT1 adsorbs miR-187-3p by sponge action, reducing miR-187-3p levels. miR-187-3p negatively regulates AGO1, and PVT1 regulates AGO1 expression by targeting miR-187-3p, thereby regulating apoptosis. In addition, we knocked down AGO1 in H9c2 cells transfected with the miR-187-3p inhibitor, and found that it inhibited apoptosis. In doxorubicin-induced cardiomyocyte toxicity, the highly expressed lncRNA PVT1 enhances the expression of AGO1 by sponge adsorption of miR-187-3p. Decreasing the expression of lncRNA PVT1 inhibits the adsorption of miR-187-3p through competing endogenous (ce) RNA, thereby reducing the expression of AGO1 and decreasing the apoptosis of cardiomyocytes. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

Jiachen Zhan, Pengfei Hu, Yujie Wang. lncRNA PVT1 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting the miR-187-3p/AGO1 axis. Molecular and cellular probes. 2020 Feb;49:101490