{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:48:50Z","timestamp":1789440530450,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["IS23101"],"award-info":[{"award-number":["IS23101"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2022YFC2705000"],"award-info":[{"award-number":["2022YFC2705000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      5\u2010Methylcytosine (m5C) RNA modification contributes to tumor initiation and progression. However, its transcriptome\u2010wide distribution patterns and biological implications in hepatitis B virus (HBV)\u2010negative hepatocellular carcinoma (HCC) remain poorly understood. Therefore, this study employs long\u2010read Nanopore direct RNA sequencing to systematically elucidate the mechanisms of m5C\u2010mediated epigenetic reprogramming in HBV\u2010negative HCC. Paired tumor and adjacent normal tissues from three HBV\u2010negative HCC patients were collected for Nanopore sequencing. Transcriptome\u2010wide m5C sites were profiled using the CHEUI tool, followed by a comprehensive comparison between tumor and adjacent normal tissue groups regarding the number of m5C sites, their genomic distribution characteristics, and the expression levels of m5C regulators. Finally, an integrated analysis of transcriptomic and methylation data was conducted to identify m5C\u2010related prognostic indicators in HCC. Tumor tissues exhibited a global increase in m5C sites abundance, with differential modifications enriched on chromosomes 1\u20133. Genes harboring m5C modifications were significantly enriched in immune and inflammatory pathways, suggesting a potential role for this epitranscriptomic mark in remodeling the tumor immune microenvironment. Consistent upregulation of m5C regulators, including\n                      <jats:italic>NSUN<\/jats:italic>\n                      family members and\n                      <jats:italic>ALYREF<\/jats:italic>\n                      , at both gene and isoform levels, correlated with increased methylation activity. Elevated m5C coupled with decreased\n                      <jats:italic>CES3<\/jats:italic>\n                      expression were associated with poorer overall survival. Additionally,\n                      <jats:italic>TMEM234<\/jats:italic>\n                      showed prognostic significance despite unchanged bulk expression in public datasets. m5C modifications are globally altered in HBV\u2010negative HCC and may contribute to post\u2010transcriptional regulation and aberrant expression. These findings highlight the potential of m5C as both a prognostic biomarker and a therapeutic target in HBV\u2010negative HCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.70080","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:04:44Z","timestamp":1769108684000},"page":"397-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The 5\u2010Methylcytosine RNA Modification in Hepatitis B Virus\u2010Negative Hepatocellular Carcinoma: Insights From Long\u2010Read Nanopore Sequencing"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1301-8164","authenticated-orcid":false,"given":"Tianhan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of General Surgery, Department of Hepato\u2010bilio\u2010pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"},{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"},{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing Hospital\/National Center of Gerontology of National Health Commission Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Science Beijing Institute of Technology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoQing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Scientific Research and Education, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital &amp; Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Xiao","sequence":"additional","affiliation":[{"name":"St. John's Northwestern Academy Delafield Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing Hospital\/National Center of Gerontology of National Health Commission Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayu","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Kuai","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanmei","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Biobank, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Department of Hepato\u2010bilio\u2010pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Data Center, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2021.1991792"},{"issue":"3","key":"e_1_2_11_3_1","article-title":"Medical Treatment of Hepatocellular Carcinoma","volume":"1","author":"Granito A.","year":"2009","journal-title":"Mediterranean Journal of Hematology and Infectious Diseases"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"261","article-title":"Recent Therapeutics in Hepatocellular Carcinoma","volume":"13","author":"Fan Z.","year":"2023","journal-title":"American Journal of Cancer 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