Jiachen Zhan1, Pengfei Hu2, Yujie Wang3. 1. Department of Cardiology, Zhuji People's Hospital of Zhejiang Province, No. 9 Jianmin Road, Tao Zhu Street, Zhuji, Zhejiang, China. 2. Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 318 Chaowang Road, Hangzhou, Zhejiang, China. 3. Department of Cardiology, Traditional Chinese Medical Hospital of Zhuji, No. 521, Donger Road, Zhuji, Zhejiang, China. Electronic address: zjzywyj@126.com.
Abstract
OBJECTIVES: To investigate the effect of long non-coding (lnc) RNA PVT1 on apoptosis induced by doxorubicin-induced cardiotoxicity. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: To investigate the effect of long non-coding (lnc) RNA PVT1 on apoptosis induced by doxorubicin-induced cardiotoxicity. METHODS: 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. RESULTS: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. CONCLUSION: 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.