{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:02:50Z","timestamp":1792123370504,"version":"4.4.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstc2021jcyj-msxmX0128"],"award-info":[{"award-number":["cstc2021jcyj-msxmX0128"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Programs of Chongqing Science and Health Union","award":["2022DBXM006"],"award-info":[{"award-number":["2022DBXM006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873702"],"award-info":[{"award-number":["81873702"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young and Middle-aged Medical Excellence Team of Chongqing","award":["cstc2022ycjh-bgzxm0126"],"award-info":[{"award-number":["cstc2022ycjh-bgzxm0126"]}]},{"name":"Chongqing Medical Scientific Research Project","award":["2021MSXM048"],"award-info":[{"award-number":["2021MSXM048"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nPurpose<\/jats:title>\nThis study investigated the effect of miR-204-5p-mediated silencing of SIRT1 on the development of deafness in C57BL\/6 mice and the roles of miR-204-5p and SIRT1 in deafness.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nAuditory brainstem response recordings, H&E staining, and immunohistochemistry were used to observe changes in hearing function and cochlear tissue morphology in 2-month-old and 15-month-old C57BL\/6 mice. A senescence model was induced using H2<\/jats:sub>O2<\/jats:sub> in inner ear cells (HEI-OC1). Changes in HEI-OC1 cell proliferation were detected using the CCK-8 assay, whereas flow cytometry was used to detect changes in apoptosis. MiR-204-5p expression was measured via RT\u2012qPCR. The SIRT1 agonist RSV and a miR-204-5p inhibitor were used to study changes in ER stress (ERS), proliferation, and apoptosis in HEI-OC1 cells. Western blotting was performed to detect changes in ATF4, CHOP, SIRT1, PERK, p-PERK, Bax, and Bcl-2 protein levels. A dual-luciferase reporter gene assay was carried out to assess the ability of miR-204-5p to target SIRT1.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nRelative miR-204-5p expression levels in the cochleae of aged C57BL\/6 mice increased, whereas SIRT1 expression levels decreased, and miR-204-5p and SIRT1 expression levels were negatively correlated. ERS and increased 8-OHDG levels were observed in aged C57BL\/6 mice. In a model of inner ear cell aging, H2<\/jats:sub>O2<\/jats:sub> treatment induced increases in miR-204-5p expression and ERS-mediated apoptosis. MiR-204-5p was found to target SIRT1 and inhibit its expression. SIRT1 activation and a miR-204-5p inhibitor promoted HEI-OC1 cell proliferation and reduced apoptosis. The miR-204-5p inhibitor regulated expression of the ERS proteins PERK, ATF4, and CHOP to upregulate Bcl-2 and downregulate Bax.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nThis study identified the roles of miR-204-5p and SIRT1 in deafness in C57BL\/6 mice and investigated the loss of cochlear outer hair cells and the involvement of apoptosis and ERS in deafness.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0309892","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T18:29:34Z","timestamp":1731436174000},"page":"e0309892","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["MiR-204-5p regulates SIRT1 to promote the endoplasmic reticulum stress-induced apoptosis of inner ear cells in C57BL\/6 mice with hearing 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