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Moreover, CPI-455 effectively prevented the death of hair cells and spiral ganglion neurons and increased the number of ribbon synapses in a cisplatin-induced ototoxicity mouse model both in vitro and in vivo. In HEI-OC1 cells, KDM5A knockdown reduced reactive oxygen species accumulation and improved mitochondrial membrane potential and oxidative phosphorylation under cisplatin-induced stress. Mechanistically, through transcriptomics and epigenomics analyses, a set of apoptosis-related genes, including <jats:italic>Sos1<\/jats:italic>, <jats:italic>Sos2<\/jats:italic>, and <jats:italic>Map3k3<\/jats:italic>, were regulated by CPI-455. Altogether, our findings indicate that inhibition of KDM5A may represent an effective epigenetic therapeutic target for preventing cisplatin-induced hearing loss.<\/jats:p>","DOI":"10.1007\/s00018-022-04565-y","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T21:03:01Z","timestamp":1668718981000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Inhibition of KDM5A attenuates cisplatin-induced hearing loss via regulation of the MAPK\/AKT pathway"],"prefix":"10.1007","volume":"79","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-372X","authenticated-orcid":false,"given":"Huawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"4565_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/187152007779314044","volume":"7","author":"V Cepeda","year":"2007","unstructured":"Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Perez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. 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