{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:45:34Z","timestamp":1776440734755,"version":"3.51.2"},"reference-count":39,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Accumulating evidence reveals that deregulated N6\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) RNA methylation and circular RNAs (circRNAs) are required for the tumorigenesis of non\u2010small cell lung cancer (NSCLC). We aimed to uncover the underlying mechanisms by which WTAP\u2010mediated m<jats:sup>6<\/jats:sup>A modification of circRNA contributes to NSCLC. The differentially\u2010expressed circRNAs were identified by a circRNA profiling microarray. The association of circSMOC1 with clinicopathological features and prognosis in patients with NSCLC was estimated by fluorescence in\u00a0situ hybridization. WTAP\u2010mediated m<jats:sup>6<\/jats:sup>A modification of circRNA was validated by RNA immunoprecipitation (RIP) and methylated RIP (MeRIP) assays. The role of circSMOC1 in NSCLC cells was validated by in\u00a0vitro functional experiments and in\u00a0vivo tumorigenesis models. CircSMOC1\u2010specific binding with miR\u2010612 was verified by RIP, luciferase gene report and RT\u2010qPCR assays. The effect of circSMOC1 and\/or miR\u2010612 on CCL28 expression was detected by RT\u2010qPCR and Western blotting analysis. We found that the expression levels of circSMOC1 were elevated in NSCLC tissues and associated with TNM stage and poor survival in patients with NSCLC. Knockdown of circSMOC1 impaired the tumorigenesis of NSCLC in\u00a0vitro and in\u00a0vivo, whereas restored expression of circSMOC1 displayed the opposite effect. Furthermore, WTAP was upregulated in NSCLC and mediated m<jats:sup>6<\/jats:sup>A modification of circSMOC1 and circSMOC1 abolished WTAP knockdown\u2010caused tumour\u2010suppressive effects. Then, circSMOC1 acted as a sponge of miR\u2010612 to upregulate CCL28 and miR\u2010612 inhibitors abrogated circSMOC1 knockdown\u2010caused anti\u2010proliferation effects and CCL28 downregulation in NSCLC cells. Knockdown of CCL28 inhibited cell proliferation and invasion and counteracted miR\u2010612 inhibitor\u2010caused tumour\u2010promoting effects. Our findings unveil that WTAP\u2010mediated m<jats:sup>6<\/jats:sup>A modification of circSMOC1 facilitates the tumorigenesis of NSCLC by regulating the miR\u2010612\/CCL28 axis.<\/jats:p>","DOI":"10.1111\/jcmm.70207","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T04:01:17Z","timestamp":1733371277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>WTAP<\/scp>\u2010Mediated <scp>m<sup>6<\/sup>A<\/scp> Modification of <scp>circSMOC1<\/scp> Accelerates the Tumorigenesis of Non\u2010Small Cell Lung Cancer by Regulating <scp>miR<\/scp>\u2010612\/<scp>CCL28<\/scp> Axis"],"prefix":"10.1111","volume":"28","author":[{"given":"Xun\u2010Xia","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Huadong Hospital, Fudan University  Shanghai 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