{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:09:02Z","timestamp":1788314942709,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Potassium voltage\u2010gated channel subfamily A regulatory beta subunit 2 (KCNAB2) is a potassium voltage\u2010gated channel subfamily A member that plays a role in non\u2010small cell lung cancer (NSCLC). However, its functional impact and mechanism in NSCLC are not fully understood. Here, we analyzed its effects on NSCLC cell behaviors and the underlying mechanism.mRNA expression levels were detected by quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR),(qRT\u2010PCR), while protein expression was quantified by western blotting blot analysis or immunohistochemistry assay. NSCLC cell proliferation, migration, invasion, macrophage polarization, and apoptosis were evaluated through cell\u2010based assays including cell counting kit\u20108 (CCK\u20108)(CCK\u20108) assay, flow cytometry, Tunel assay, wound\u2010healing assay, and transwell invasion assay. The role of FTO alpha\u2010ketoglutarate dependent dioxygenase (FTO)\u2010mediated(FTO)\u2010mediated m6A methylation in the regulation of KCNAB2 expression and their impacts on NSCLC cell behavior and M2 macrophage polarization were assessed through m6A RNA immunoprecipitation assay and rescue experiments. Xenograft mouse model assay was used to determine the effect of KCNAB2 on tumor formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    .in vivo.KCNAB2 expression was downregulated and FTO expression was upregulated in NSCLC tissues and cells when compared with controls. Moreover, the expression of KCNAB2 was found to be lower in stage III NSCLC patients compared to those at stages I and II, and it was also lower in patients with positive lymph node metastasis compared to those with negative lymph node metastasis. Overexpression of KCNAB2 inhibited NSCLC cell proliferation, migration, invasion, and M2 macrophage polarization, while inducing cell apoptosis. These effects were mediated, at least partially, by inactivating the phosphoinositide 3\u2010kinase (PI3K)\/AKT(PI3K)\/AKT pathway. Moreover, ectopic expression of KCNAB2 delayed tumor formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . FTOin vivo. FTO was found to mediate m6A methylation of KCNAB2, and knockdown of FTO resulted in the upregulation of KCNAB2 expression, leading to inhibition of NSCLC cell behavior and M2 macrophage polarization.KCNAB2 overexpression inhibited NSCLC cell behavior and M2 macrophage polarization by inactivating the PI3KPI3K\/AKT\/AKT pathway. Furthermore, FTOFTO\u2010mediated\u2010mediated m6A methylation was involved in the regulation of KCNAB2 expression in NSCLC. These results enhance our understanding of the role of KCNAB2 in NSCLC and suggest its potential as a therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70232","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T05:35:32Z","timestamp":1742708132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["FTO\u2010mediated m6A Methylation of KCNAB2 Inhibits Tumor Property of Non\u2010Small Cell Lung Cancer Cells and M2 Macrophage Polarization by Inactivating the PI3K\/AKT Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Yanguang","family":"Li","sequence":"first","affiliation":[{"name":"Department of thoracic surgery Cangzhou Central Hospital Cangzhou City Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieting","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of geriatric internal medicine Cangzhou Central Hospital Cangzhou City Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of thoracic surgery, Cangzhou Hospital of Integrated TCM\u2010WM Cangzhou City Hebei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7133-3367","authenticated-orcid":false,"given":"Junfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department 3 of thoracic The Fourth Hospital of Hebei Medical University Shijiazhuang City Hebei Province 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