{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:19:01Z","timestamp":1787818741044,"version":"build-2784847793"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Nantong University Special Research Fund for Clinical Medicine","award":["2025LQ021"],"award-info":[{"award-number":["2025LQ021"]}]},{"name":"China Postdoctoral Science Foundation General Project"},{"name":"Research on the Role and Mechanism of Lung Cancer-Derived Exosome Circular","award":["RNA-circ10824"],"award-info":[{"award-number":["RNA-circ10824"]}]},{"name":"Tumor Cachexia Skeletal Muscle Atrophy","award":["2022M721725"],"award-info":[{"award-number":["2022M721725"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>As a 5-methylcytosine (m5C) methyltransferase, increased NOP2\/Sun RNA methyltransferase 2 (NSUN2) has been revealed to promote the progression of non-small cell lung cancer (NSCLC) through m5C modification. Herein, this study aimed to investigate the potential molecular mechanisms underlying the high NSUN2 expression in NSCLC, and the potential downstream m5C mRNAs of NSUN2 in promoting NSCLC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Measurements<\/jats:title>\n                    <jats:p>Functional analyses were conducted using in vitro 3- (4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2\u2032-deoxyuridine, Transwell, wound healing, and sphere and tube formation assays, and an in vivo murine model. m5C modification was determined by m5C-methylated RNA immunoprecipitation assay. RNA immunoprecipitation assay determined the binding between NSUN2 and SLC7A5 mRNA. The upstream molecular mechanism of the upregulation of NSUN2 expression was explored using chromatin immunoprecipitation, co-immunoprecipitation, and luciferase reporter assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Results<\/jats:title>\n                    <jats:p>NSUN2 was highly expressed in NSCLC and predicted poor outcomes in NSCLC patients. Functionally, NSUN2 silencing suppressed cancer cell proliferation, migration, stemness properties, angiogenic ability, and glutamine metabolism. Mechanistically, NSUN2 induced m5C methylation modification of SLC7A5, and stabilized SLC7A5 mRNA via a YBX1-dependent mechanism. Accordingly, SLC7A5 overexpression reversed the anticancer effects of NSUN2 on above oncogenic phenotypes. Further upstream molecular mechanism analysis showed that P300 could bind to and cooperate with transcription factor SP1 to increase NSUN2 expression by histone H3 lysine 27 acetylation (H3K27ac). Further in vivo analyses suggested that NSUN2 silencing suppressed NSCLC growth and metastasis in vivo by regulating SLC7A5 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased NSUN2 derived by P300\/SP1 complex-mediated histone acetylation promoted the growth, metastasis, and glutamine metabolism of NSCLC by stabilizing SLC7A5 mRNA via m5C modification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1165\/rcmb.2025-0274oc","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T20:03:21Z","timestamp":1760472201000},"page":"1267-1281","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["NSUN2 promotes the growth, metastasis, and glutamine metabolism of non-small cell lung 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Nantong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Affiliated Nantong Clinical College of Nantong University, The First People's Hospital of Nantong, 226001, Nantong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Affiliated Nantong Clinical College of Nantong University, The First People's Hospital of Nantong, 226001, Nantong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Affiliated Nantong Clinical College of Nantong University, The First People's Hospital of Nantong, 226001, 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