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Chongqing Natural Science Foundation","award":["cstc2021jcyj-bshx0026"],"award-info":[{"award-number":["cstc2021jcyj-bshx0026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Age-related hearing loss (ARHL), also known as presbycusis, is one of the most common neurodegenerative disorders in elderly individuals and has a prevalence of approximately 70\u201380% among individuals aged 65 and older. As ARHL is an intricate and multifactorial disease, the exact pathogenesis of ARHL is not fully understood. There is evidence that transcriptional dysregulation mediated by epigenetic modifications is widespread in ARHL. However, the potential role of N6-methyladenosine (m6A) modification, as a crucial component of epigenetics, in ARHL progression remains unclear. In this study, we confirmed that the downregulation of m6A modification in cochlear tissues is related to ARHL and found that the expression of the m6A methylation regulators Wilms tumour suppressor-1-associated protein (WTAP), methyltransferase-like 3 (METTL3), ALKB homologous protein 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) is decreased significantly at the mRNA and protein levels in ARHL mice. Then, we used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) to identify the differentially m6A-methylated genes in the cochlear tissues of ARHL mice. A total of 3438 genes with differential m6A methylation were identified, of which 1332 genes were m6A-hypermethylated and 2106 genes were m6A-hypomethylated in the ARHL group compared to the control group according to MeRIP-seq. Further joint analysis of RNA-Seq and MeRIP-Seq data showed that 262 genes had significant differences in both mRNA expression and m6A methylation. GO and KEGG analyses indicated that 262 unique genes were enriched mainly in the PI3K-AKT signalling pathway. In conclusion, the results of this study reveal differential m6A methylation patterns in the cochlear tissues of ARHL mice, providing a theoretical basis for further study of the pathogenesis of ARHL and potential therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom13101537","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:55:06Z","timestamp":1697622906000},"page":"1537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss"],"prefix":"10.3390","volume":"13","author":[{"given":"Menglong","family":"Feng","sequence":"first","affiliation":[{"name":"Chongqing Medical University, Chongqing 400016, China"},{"name":"Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Chongqing School, University of Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Medical University, Chongqing 400016, China"},{"name":"Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Chongqing School, University of Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiji","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Chongqing Medical University, Chongqing 400016, China"},{"name":"Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Chongqing School, University of Chinese Academy of Sciences, Chongqing 400714, China"},{"name":"Department of Otolaryngology & Head and Neck, Chongqing General Hospital, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1044\/2019_AJA-18-0152","article-title":"Characteristics of Adults with Unrecognized Hearing Loss","volume":"28","author":"Rapport","year":"2019","journal-title":"Am. 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