miR‑34a induces apoptosis and pyroptosis in D‑Galactose‑induced aging cochlear hair cells via inhibiting TFAM and promoting mitochondrial dysfunction <em>in vitro</em> and <em>in vivo</em>

Wang,Yilan; Yang,Ming; Wang,Guihua; Liu,Weimin; Deng,Bin; Yang,Xiaoran; Li,Xuzhao

doi:10.3892/ijmm.2025.5541

miR‑34a induces apoptosis and pyroptosis in D‑Galactose‑induced aging cochlear hair cells via inhibiting TFAM and promoting mitochondrial dysfunction in vitro and in vivo

Authors:
- Yilan Wang
- Ming Yang
- Guihua Wang
- Weimin Liu
- Bin Deng
- Xiaoran Yang
- Xuzhao Li
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Affiliations: Department of Otolaryngology Head and Neck Surgery, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui 750002, P.R. China, Department of Emergency Medicine, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui 750002, P.R. China, Department of General Surgery, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia Hui 750002, P.R. China
Published online on: April 30, 2025 https://doi.org/10.3892/ijmm.2025.5541
Article Number: 100
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aging of the auditory system causes progressive hearing deficit and affects millions of people; however, the underlying mechanism remains largely unknown. D‑galactose (D‑gal)‑induced aging models were established in vitro using HEI‑OC1 cells and in vivo using C57BL/6 mice to investigate the role of miR‑34a in age‑related hearing loss (ARHL). HEI‑OC1 cells were treated with D‑gal for, while mice received daily intraperitoneal injections of D‑gal for six weeks. Molecular and functional analyses, including reverse transcription‑quantitative PCR, Western blot, flow cytometry, immunofluorescence, and dual‑luciferase reporter assays, were performed to evaluate oxidative stress, mitochondrial dysfunction, apoptosis, and pyroptosis, with miR‑34a inhibitor and DRP1 inhibitor (Mdivi‑1) used to assess their regulatory effects. D‑gal induced hair cell loss by apoptosis and pyroptosis, which was modulated by microRNA (miR)‑34a via mitochondrial dysfunction in vitro and in vivo. Inhibition of mitochondrial transcription factor A (TFAM), which is the target gene of miR‑34a, was involved in the underlying molecular mechanism. miR‑34a mediated apoptosis and pyroptosis in D‑gal‑induced cochlear hair cells via inhibiting TFAM and promoting mitochondrial dysfunction in vitro and in vivo and may serve as a new potential target for future ARHL treatment.

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