MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a

MiR-182-5p 通过抑制 FOXO3a 保护内耳毛细胞免受顺铂诱导的细胞凋亡

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作者:Yimeng Li, Ao Li, Jingfang Wu, Yingzi He, Huiqian Yu, Renjie Chai, Huawei Li

Abstract

Cisplatin is widely used for chemotherapy of a variety of malignancies. However, the clinical application of cisplatin is hampered by the resultant irreversible hearing loss due to hair cell apoptosis. To date, no practical regimen to resolve this has been developed. Meanwhile, the role of microRNA in protecting hair cells from cisplatin-induced apoptosis in the inner ear has not been extensively investigated. In this study, we monitored miR-183, -96, and -182 turnover in the cochlea during cisplatin treatment in vitro. We found that overexpression of miR-182, but not miR-183 and -96, improved hair cell survival after 3 μM cisplatin treatment in vitro. We demonstrated that overexpression of miR-182 repressed the intrinsic apoptotic pathway by inhibiting the translation of FOXO3a. Our study offers a new therapeutic target for alleviating cisplatin-induced hair cell apoptosis in a rapid and tissue-specific manner.

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