Cardiotoxicity is one of the primary limitations in the clinical use of the anticancer drug doxorubicin (DOX). However, the role of microRNAs (miRNAs) in DOX-induced cardiomyocyte death has not yet been covered. To investigate this, we observed a significant increase in miR-98 expression in neonatal rat ventricular myocytes after DOX treatment, and MTT, LIVE/Dead and Viability/Cytotoxicity staining showed that miR-98 mimic inhibited DOX-induced cell death. This was also confirmed by Flow cytometry and Annexin V-FITC/PI staining. Interestingly, the protein expression of caspase-8 was upregulated by miR-98 mimics during this process, whereas Fas and RIP3 were downregulated. In addition, the effect of miR-98 against the expression of Fas and RIP3 were restored by the specific caspase-8 inhibitor Z-IETD-FMK. Thus, we demonstrate that miR-98 protects cardiomyocytes from DOX-induced injury by regulating the caspase-8-dependent Fas/RIP3 pathway. Our findings enhance understanding of the therapeutic role of miRNAs in the treatment of DOX-induced cardiotoxicity.

心脏毒性是抗癌药物多柔比星 (DOX) 临床使用的主要限制之一。然而，microRNAs (miRNAs) 在 DOX 诱导的心肌细胞死亡中的作用尚未涵盖。为了研究这一点，我们观察到 DOX 治疗后新生大鼠心室肌细胞中 miR-98 表达显着增加，并且 MTT、LIVE/Dead 和活力/细胞毒性染色表明 miR-98 模拟物抑制了 DOX 诱导的细胞死亡。这也通过流式细胞术和膜联蛋白 V-FITC/PI 染色得到证实。有趣的是，在此过程中，miR-98 模拟物上调了 caspase-8 的蛋白质表达，而 Fas 和 RIP3 则下调。此外，特异性 caspase-8 抑制剂 Z-IETD-FMK 恢复了 miR-98 对 Fas 和 RIP3 表达的影响。因此，我们证明 miR-98 通过调节 caspase-8 依赖性 Fas/RIP3 通路保护心肌细胞免受 DOX 诱导的损伤。我们的发现增强了对 miRNA 在治疗 DOX 诱导的心脏毒性中的治疗作用的理解。