FTO‐mediated m6A Methylation of KCNAB2 Inhibits Tumor Property of Non‐Small Cell Lung Cancer Cells and M2 Macrophage Polarization by Inactivating the PI3K/AKT Pathway

作者：Yan‐Guang Li, Jieting Niu, Zhiguang Sun, Junfeng Liu · 发表于：Journal of Biochemical and Molecular Toxicology · 年份：2025 · DOI：10.1002/jbt.70232 · 被引用次数：6 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Peptidase Inhibition and Analysis

Potassium voltage-gated channel subfamily A regulatory beta subunit 2 (KCNAB2) is a potassium voltage-gated channel subfamily A member that plays a role in non-small 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-time polymerase chain reaction (qRT-PCR),(qRT-PCR), 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-based assays including cell counting kit-8 (CCK-8)(CCK-8) assay, flow cytometry, Tunel assay, wound-healing assay, and transwell invasion assay. The role of FTO alpha-ketoglutarate dependent dioxygenase (FTO)-mediated(FTO)-mediated 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 in vivo.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...