{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:24:07Z","timestamp":1770891847677,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Cellular senescence, a stress\u2010induced cell cycle arrest state, plays a dual role in cancer. Circular RNAs (circRNAs), endogenous noncoding RNAs, regulate physiological processes and are linked to diseases including cancer. This study investigates the role and mechanism of circPTK2 in non\u2010small cell lung cancer (NSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Lentivirus\u2010mediated knockdown or overexpression of circPTK2 were used to assess effects on proliferation and senescence. circPTK2 expression in NSCLC tissues was examined using tissue microarrays and in situ hybridization. RNA\u2010seq identified circPTK2\u2010regulated signalling pathways and downstream targets. Transcriptional regulation of FOXM1 by NFYA was investigated using chromatin immunoprecipitation (ChIP) and dual\u2010luciferase reporter assays. Co\u2010immunoprecipitation (Co\u2010IP) was conducted to assess the interaction between NFYA and MDM2, as well as NFYA ubiquitination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>circPTK2 was highly expressed in NSCLC tissues and was associated with poor prognosis. Knockdown of circPTK2 significantly inhibited cancer cell growth and enhanced cellular senescence. RNA\u2010seq analysis identified FOXM1 as a downstream target of circPTK2. Database predictions suggested that NFYA could transcriptionally regulate FOXM1. Knockdown of circPTK2 induced NFYA degradation. circPTK2 was found to bind to the E3 ubiquitin ligase MDM2 in the cytoplasm, thereby preventing MDM2 from interacting with the transcription factor NFYA. This interaction blocked MDM2\u2010mediated ubiquitylation and degradation of NFYA. Additionally, NFYA bound to the FOXM1 gene promoter, ultimately leading to the up\u2010regulation of FOXM1 and suppression of cellular senescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Elevated circPTK2 expression correlates with poorer survival, representing a potential therapeutic target in NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70220","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T06:51:39Z","timestamp":1762584699000},"page":"1085-1103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CircPTK2 enhances non\u2010small cell lung cancer proliferation by inhibiting cellular senescence through stabilizing NFYA and elevating 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