MiR-34a/DRP-1-mediated Mitophagy Participated in Cisplatin-induced Ototoxicity Via Increasing Oxidative Stress
Overview
Authors
Affiliations
Purpose: Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity.
Methods: In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy.
Results: MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function.
Conclusion: MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.
Dai D, Chen C, Lu C, Guo Y, Li Q, Sun C Front Pharmacol. 2024; 15:1430469.
PMID: 39380912 PMC: 11459463. DOI: 10.3389/fphar.2024.1430469.
Liu W, Li R, Le Y, Zhu Z Heliyon. 2024; 10(15):e35305.
PMID: 39170577 PMC: 11336613. DOI: 10.1016/j.heliyon.2024.e35305.
Hesperidin activates Nrf2 to protect cochlear hair cells from cisplatin-induced damage.
Lou J, Wu F, He W, Hu R, Cai Z, Chen G Redox Rep. 2024; 29(1):2341470.
PMID: 38629504 PMC: 11025410. DOI: 10.1080/13510002.2024.2341470.
NcRNA: key and potential in hearing loss.
Zhu K, Wang T, Li S, Liu Z, Zhan Y, Zhang Q Front Neurosci. 2024; 17:1333131.
PMID: 38298898 PMC: 10827912. DOI: 10.3389/fnins.2023.1333131.
Katanic Stankovic J, Selakovic D, Rosic G Int J Mol Sci. 2023; 24(19).
PMID: 37834021 PMC: 10572959. DOI: 10.3390/ijms241914574.