Downregulating miR-432-5p exacerbates adriamycin-induced cardiotoxicity via activating the RTN3 signaling pathway

下调 miR-432-5p 通过激活 RTN3 信号通路加剧阿霉素引起的心脏毒性

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作者:Wei Geng, Shaohua Yan, Dasen Sang, Jie Tao, Xuefei Zhang, Xinshun Gu, Xiangyu Zhang

Background

Adriamycin (ADR) is a widely used chemotherapy drug in clinical practice and it causes toxicity in the myocardium affecting its clinical use. miR-432-5p is a miRNA primarily expressed in myocardial cells and has a protective effect in the myocardium. We

Conclusion

ADR can induce the low expression of miR-432-5p, and activate the RTN3 pathway in ER, increase the expression of LC3B, Beclin 1, cleaved caspase 3, CHOP, and RTN3, and induce cardiac toxicity.

Results

ADR decreased the expression of miR-432-5p in cardiomyocytes. It also decreases mitochondrial ATP production and activates the ER stress pathway by increasing the expression of LC3B, Beclin 1, cleaved caspase 3, and induces cardiac toxicity. miR-432-5p exogenous supplementation can reduce the cardiotoxicity caused by ADR, and its protective effect on cardiomyocytes depends on the down-regulation of the RTN3 signaling pathway in ER.

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