{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:09:05Z","timestamp":1777910945168,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103285"],"award-info":[{"award-number":["82103285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFB824"],"award-info":[{"award-number":["2023AFB824"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteosarcoma, the most common primary malignant bone tumor with poor prognosis, underscores the need for a deeper understanding of its molecular mechanisms. Recent studies have highlighted the importance of RNA modifications, including 5\u2010methylcytosine (m5C), in cancer progression, yet the m5C modification landscape in osteosarcoma remains unexplored. Here, we performed transcriptome\u2010wide profiling of m5C modifications in osteosarcoma using meRIP\u2010seq and RNA\u2010seq, analyzing four pairs of osteosarcoma and adjacent normal tissues. Furthermore, through conjunction analyses of meRIP\u2010seq and RNA\u2010seq data, we identified 637 genes with significant changes in both the m5C modification and mRNA levels. Among these, GPRC5B emerged as a key prognostic gene, with its high expression and m5C hypermethylation significantly associated with poor survival in osteosarcoma patients. Functional experiments demonstrated that GPRC5B suppresses apoptosis and promotes osteosarcoma cell proliferation and migration. Mechanistically, NSUN2\u2010mediated m5C modification upregulates GPRC5B expression, and the anti\u2010apoptotic effects of NSUN2 are primarily dependent on its ability to modulate GPRC5B m5C modification and expression. Knockdown of GPRC5B partially rescues the anti\u2010apoptotic effects of NSUN2, highlighting the critical role of GPRC5B in osteosarcoma survival. Our study identified an m5C\u2010dependent NSUN2\u2010GPRC5B regulatory axis, providing insights into osteosarcoma progression and revealing its therapeutic potential.<\/jats:p>","DOI":"10.1111\/cas.70362","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:21:32Z","timestamp":1773818492000},"page":"1322-1332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>GPRC5B<\/scp>\n                    Identified by\n                    <scp>m5C meRIP<\/scp>\n                    \u2010Seq Suppresses Apoptosis in Osteosarcoma Through\n                    <scp>NSUN2<\/scp>\n                    \u2010Mediated\n                    <scp>RNA<\/scp>\n                    Methylation"],"prefix":"10.1111","volume":"117","author":[{"given":"Zhenyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of China"},{"name":"Department of Orthopedics Jingzhou Hospital Affiliated to Yangtze University  Jingzhou Hubei People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Bone and Soft Tissue Oncology Affiliated Tumor Hospital of Zhengzhou University  Zhengzhou People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of 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of Wuhan University  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanhang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanlong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-6429","authenticated-orcid":false,"given":"Lin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  Wuhan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19860401)57:7<1442::AID-CNCR2820570734>3.0.CO;2-3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0284-9_2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082130"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13122878"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00409-y"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-016-0050-2"},{"key":"e_1_2_12_8_1","first-page":"1099","article-title":"Biology and Pathogenesis of Human Osteosarcoma","volume":"19","author":"Azevedo J.","year":"2020","journal-title":"Oncology 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