title: Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss.
abstract: The molecular mechanisms underlying age-related hearing loss are not fully understood, and currently, there is no treatment for this disorder. MicroRNAs have recently been reported to be increasingly associated with age-related diseases and are emerging as promising therapeutic targets. In this study, miR-34a/Sirtuin 1 (SIRT1)/p53 signaling was examined in cochlear hair cells during aging. MiR-34a, p53 acetylation, and apoptosis increased in the cochlea of C57BL/6 mice with aging, whereas an age-related decrease in SIRT1 was observed. In the inner ear HEI-OC1 cell line, miR-34a overexpression inhibited SIRT1, leading to an increase in p53 acetylation and apoptosis. Moreover, miR-34a knockdown increased SIRT1 expression and diminished p53 acetylation, and apoptosis. Additionally, resveratrol, an activator of SIRT1, significantly rescued miR-34a overexpression-induced HEI-OC1 cell death and significantly reduced hearing threshold shifts and hair cell loss in C57BL/6 mice after a 2-month administration. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/SIRT1/p53 signaling, which may serve as a potential target for age-related hearing loss treatment.
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Hao
authors: H
authors: Xiong
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Jiaqi
authors: J
authors: Pang
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Haidi
authors: H
authors: Yang
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Min
authors: M
authors: Dai
authors: Guangzhou Occupational Disease Prevention and Treatment Center, Guangzhou, China.
authors: Yimin
authors: Y
authors: Liu
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Yongkang
authors: Y
authors: Ou
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Qiuhong
authors: Q
authors: Huang
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Suijun
authors: S
authors: Chen
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Zhigang
authors: Z
authors: Zhang
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Yaodong
authors: Y
authors: Xu
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
authors: Lan
authors: L
authors: Lai
authors: Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China. Electronic address: yiqingzheng@hotmail.com.
authors: Yiqing
authors: Y
authors: Zheng
mesh_terms: D000107:Acetylation; D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D015870:Gene Expression; D006198:Hair Cells, Auditory / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy / Q000473:pathology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D056564:Sirtuin 1 / Q000378:metabolism / Q000502:physiology*; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Cochlea; MicroRNA; Presbycusis; SIRT1; p53