{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T18:36:02Z","timestamp":1768242962232,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy\u2019s Hundred Disciplinary Talents Program","award":["2025022106"],"award-info":[{"award-number":["2025022106"]}]},{"name":"Senior Medical Talents Program of Chongqing for Young and Middle-aged"},{"name":"Fundamental Research Funds for the Central","award":["2025CDJZKCGJ-08"],"award-info":[{"award-number":["2025CDJZKCGJ-08"]}]},{"name":"Chongqing Technology Innovation and Application Development Special Project","award":["CSTB2023TIAD-KPX0059"],"award-info":[{"award-number":["CSTB2023TIAD-KPX0059"]}]},{"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":"Major Programs of Chongqing Science and Health Union","award":["2022DBXM006"],"award-info":[{"award-number":["2022DBXM006"]}]},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Beijing, China","award":["2024KF008"],"award-info":[{"award-number":["2024KF008"]}]},{"name":"Hearing, Speech, and Cognition Laboratory"},{"name":"The Natural Science Foundation of Chongqing of China","award":["CSTB2024NSCQ-MSX0871"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0871"]}]},{"name":"The Natural Science Foundation of Chongqing of China","award":["CSTB2024JXJL-YFX0023"],"award-info":[{"award-number":["CSTB2024JXJL-YFX0023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objectives: To systematically analyze the expression profiles of long non-coding RNAs (lncRNAs) in serum-derived exosomes from patients with age-related hearing loss (ARHL), and to further identify key regulatory lncRNAs involved in the pathogenesis and progression of ARHL. Methods: Peripheral blood samples were collected from patients with ARHL and age-matched normal-hearing controls. Serum was separated and exosomes were extracted. The exosomes were identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blot. Subsequently, total RNA was extracted from the purified exosomes for lncRNA transcriptome sequencing. Based on the sequencing results, we identified differentially expressed lncRNAs and mRNAs and conducted multi-dimensional functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database (Reactome), and Disease Ontology (DO). Finally, four key mRNAs (THAP2, ZNF225, MED12, and RNF141) and four differentially expressed lncRNAs (DE-lncRNAs), namely MSTRG.150961.7, ENSG00000273015, MSTRG.336598.1, and ENSG00000273493, were experimentally verified by quantitative real-time polymerase chain reaction (RT-qPCR) technology. Results: Exosomes were successfully isolated from serum and confirmed by particle size, morphological examination, and the expression of exosome-labeled proteins. A total of 2874 DE-lncRNAs were identified, among which 988 were downregulated and 1886 were upregulated. Similarly, 2132 DE-mRNAs were detected, among which 882 were downregulated and 1250 were upregulated. GO analysis revealed significant enrichment in biological processes such as \u201cphospholipid binding\u201d, \u201cphosphatidylinositol binding\u201d, \u201cphosphatase binding\u201d, \u201cphosphatidylinositol bisphosphate binding\u201d, \u201cphosphatidylinositol-4,5-bisphosphate binding\u201d, \u201cphosphatidylinositol-3,5-bisphosphate phosphatase activity\u201d. KEGG is significantly enriched in signaling pathways including \u201cWnt signaling pathway\u201d, \u201cHippo signaling pathway\u201d, \u201cCushing syndrome\u201d, and \u201cNucleocytoplasmic transport\u201d. The functional annotations of Reactome were significantly enriched in biomolecular pathways including \u201ctRNA processing\u201d, \u201cCellular response to heat stress\u201d, \u201cExtra-nuclear estrogen signaling\u201d, \u201cMetabolism of non-coding RNA\u201d, and \u201cCTNNB1 T41 mutants aren\u2019t phosphorylated\u201d. DO is significantly enriched in diseases or pathological conditions such as \u201chepatitis\u201d, \u201cbacterial infectious disease\u201d, \u201ccystic fibrosis\u201d, and \u201cvasculitis\u201d. Conclusions:THAP2, ZNF225, MED12, and RNF141 may serve as potential candidate biomarker for ARHL. Additionally, lncRNA MSTRG.150961.7, lncRNA MSTRG.336598.1, and lncRNA ENSG00000273493 may play significant roles in the pathogenesis of this condition.<\/jats:p>","DOI":"10.3390\/diagnostics16020248","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:57:25Z","timestamp":1768229845000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Whole Transcriptome Sequencing Profile of Serum-Derived Exosomes and Potential Pathophysiology of Age-Related Hearing Loss"],"prefix":"10.3390","volume":"16","author":[{"given":"Guijun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongqin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Xinqiao Community Health Service Center, Shapingba District, Chongqing 400030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-4323","authenticated-orcid":false,"given":"Jing","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Tang","sequence":"additional","affiliation":[{"name":"CQMPA Key Laboratory for Development and Evaluation of Innovative Biological Products, Chongqing 401121, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiji","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaojing","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feixian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"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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