{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:57Z","timestamp":1786566537722,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The lncRNA SH3PXD2A\u2010AS1 drives therapy resistance in non\u2010small cell lung cancer (NSCLC) through m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010mediated PD\u2010L1 overexpression, representing a novel molecular toxicology paradigm. In the present work, the functional significance of SH3PXD2A\u2010AS1 in orchestrating immune escape and malignant progression of NSCLC was systematically examined. Integrating TCGA analyses with cell and mouse studies, we found that SH3PXD2A\u2010AS1 was elevated in NSCLC and associated with features of an immunosuppressive tumor microenvironment. Multi\u2010omics profiling, RNA pull\u2010down\/RIP, and promoter\u2010reporter assays revealed that SH3PXD2A\u2010AS1 interacts with the transcription factor MYBL2 to drive transcriptional activation of WTAP, a core component of the m\n                    <jats:sup>6<\/jats:sup>\n                    A writer complex. This axis enhanced m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of PD\u2010L1 mRNA, stabilizing PD\u2010L1 and dampening CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell responses. Silencing SH3PXD2A\u2010AS1 reduced MYBL2\/WTAP\/PD\u2010L1 signaling, decreased malignant phenotypes\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and restored antitumor T\u2010cell activity in humanized mouse models, whereas enforced MYBL2 or WTAP expression counteracted these effects. Collectively, these findings define an lncRNA\u2013transcription factor\u2013epitranscriptomic checkpoint that sustains PD\u2010L1\u2013mediated immune escape in NSCLC, and nominate SH3PXD2A\u2010AS1 and its MYBL2\/WTAP partners as potential biomarkers and therapeutic targets to improve responses to immune checkpoint inhibition.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70784","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:27:26Z","timestamp":1776666446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicological Implications of m\n                    <sup>6<\/sup>\n                    A Dysregulation: SH3PXD2A\u2010AS1\u2010Driven PD\u2010L1 Overexpression Promotes Immune Evasion in NSCLC"],"prefix":"10.1002","volume":"40","author":[{"given":"Siyan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingchuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and 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