Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.
Biosci Rep. 2019 Jul 25;39(7). doi: 10.1042/BSR20191050. Print 2019 Jul 31.
Doxorubicin (DOX) is a highly effective anti-tumor drug, but its cardiotoxicity largely restricts its clinical application. The present study was designed to explore whether DOX toxicity in AC16 cardiomyocytes can be regulated by long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) and to elucidate the underlying mechanisms. We found that DOX treatment led to severe damage in AC16 cells through decreasing cell viability and increasing cell apoptosis. DOX treatment also reduced the expression of SNHG1 in AC16 cells, and overexpression of SNHG1 alleviated the increased apoptosis in DOX-treated AC16 cells. Moreover, we found that SNHG1 could counteract the inhibitory effect of miR-195 on Bcl-2, and miR-195 restoration blocked the beneficial effect of SNHG1 against DOX toxicity in AC16 cells. In short, the present study provided convincing evidence that SNHG1 protects human AC16 cardiomyocytes from DOX toxicity partly by regulating miR-195/Bcl-2 axis.
多柔比星（DOX）是一种高效的抗肿瘤药物，但它的心脏毒性在很大程度上限制了其临床应用。本研究旨在探讨长链非编码 RNA（lncRNA）小核仁 RNA 宿主基因 1（SNHG1）是否可以调节 AC16 心肌细胞中的 DOX 毒性，并阐明其潜在机制。我们发现 DOX 处理通过降低细胞活力和增加细胞凋亡导致 AC16 细胞严重损伤。DOX 处理还降低了 AC16 细胞中 SNHG1 的表达，而过表达 SNHG1 减轻了 DOX 处理的 AC16 细胞中增加的细胞凋亡。此外，我们发现 SNHG1 可以抵消 miR-195 对 Bcl-2 的抑制作用，而 miR-195 的恢复阻断了 SNHG1 对 AC16 细胞中 DOX 毒性的有益作用。总之，本研究提供了令人信服的证据，表明 SNHG1 通过调节 miR-195/Bcl-2 轴部分保护人 AC16 心肌细胞免受 DOX 毒性。
