Dataset Information

Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss.

ABSTRACT: 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 70-80% 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.

SUBMITTER: Feng M

PROVIDER: S-EPMC10605720 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss.

Feng Menglong M Zhou Xiaoqing X Hu Yaqin Y Zhang Juhong J Yang Ting T Chen Zhiji Z Yuan Wei W

Biomolecules 20231018 10

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 70-80% 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) modi ...[more]

PMID: 37892219

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Project description:BackgroundOur study aimed to determine the pathological mechanism of presbycusis at the molecular level, and determine potential biomarkers for the same.MethodsDifferentially expressed genes (DEGs) for presbycusis were obtained by analyzing the microarray data sets (GSE6045 and GSE49543) downloaded from the Gene Expression Omnibus (GEO). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway, and protein-protein interaction (PPI) network analyses, and Gene Set Enrichment Analysis (GSEA) were performed to analyze the biological functions, molecular pathways, autophagy-related molecular markers, and the immune microenvironment of the DEGs in presbycusis. Then the prognostic roles of the hub genes were analyzed and verified in vivo.ResultsIn the old mild hearing loss group (27.7 ± 3.4 months old), 27 down-regulated and 99 up-regulated genes were significantly differentially expressed compared with those in the young control group (3.5 ± 0.4 months old). In the old severe hearing loss group (30.6 ± 1.9 months old), 131 down-regulated and 89 up-regulated genes were significantly differentially expressed compared with those in the young control group. The results of the GO, GSEA, KEGG pathway, and immune infiltration analyses showed that the enrichment terms were mainly focused on immune response in mild presbycusis, and immune response and cell death in severe presbycusis. In the PPI network, autophagy-related genes ATG5, ATG7 showed the highest node scores in mild presbycusis; whereas MTOR, BECN1 showed the highest scores in severe presbycusis. In the GSE49543 data set, four genes (Ywhag, Mapre2, Fgf1, Acss2) were used to construct the prognostic model, and those four genes were significantly up-regulated in the rat model of presbycusis.ConclusionOur study is the first to report the difference in autophagy factors and immune microenvironment among different degrees of hearing loss in presbycusis. Furthermore, we provide the prognostic gene expression signature for age-related hearing loss, intending to develop preventative therapies.

Dataset Information

Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss.

Publications

Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss.

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