MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a.
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.
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Yimeng
Y
Li
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Ao
A
Li
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Jingfang
J
Wu
Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Central Laboratory, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Yingzi
Y
He
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.
Huiqian
H
Yu
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Renjie
R
Chai
Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Key Laboratory for Hearing Science, Ministry of Health, Affiliated Eye and ENT Hospital of Fudan University, Shanghai 200031, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Huawei
H
Li
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002945:Cisplatin / Q000633:toxicity*; D000071316:Forkhead Box Protein O3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D002867:Chromones; D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; C543802:Mirn183 microRNA, mouse; C541554:Mirn96 microRNA, mouse; D009025:Morpholines; D020320:Oligoribonucleotides, Antisense; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002945:Cisplatin