空军军医大学学报2025，Vol.46Issue(7)：900-905,912,7.DOI:10.13276/j.issn.2097-1656.2025.07.009
BAK1 m6A甲基化修饰在乳腺癌细胞失巢凋亡中的作用和机制研究
The m6A modification mechanism of BAK1 and its role in anoikis of breast cancer cells
摘要
Abstract
Objective To investigate the m6A modification mechanism of BAK1 and its role in anoikis of breast cancer cells,in order to elucidate the molecular mechanisms of anoikis resistance and provide new therapeutic targets for breast cancer.Methods An anoikis model was established using low-adhesion culture methods.Cell samples were collected for subsequent experiments after 0,24,48,and 72 h of low-adhesion treatment.Triple-negative breast cancer cells(MDA-MB-231)and non-triple-negative breast cancer cells(T47D)were used as research subjects.Apoptosis rates were detected by Annexin V-FITC/PI double staining,changes in m6A levels were measured by Dot blot assays,and the expression levels of related proteins and genes were analyzed by Western blotting and qRT-PCR.Results T47D had significantly increased apoptosis rates after low-adhesion treatment(P＜0.01),while MDA-MB-231 exhibited strong anoikis resistance.Anoikis induced an increase in m6A levels in non-triple-negative breast cancer cells(P＜0.01),mainly mediated by changes in the expression of the demethylase FTO.Inhibition of m6A modification significantly enhanced the anoikis resistance of breast cancer cells(P＜0.05),and m6A modification affected apoptosis sensitivity by regulating the expression of BAK1.Conclusion This study reveals the important role of m6A modification in anoikis of breast cancer cells and its mechanism through regulating BAK1 expression,providing a new perspective for understanding the invasion and metastasis mechanisms of breast cancer cells and potentially offering a theoretical basis for developing new therapeutic strategies and prognostic biomarkers.关键词
乳腺癌/失巢凋亡/信使RNA/甲基化/凋亡调节蛋白/肿瘤基因表达调控/肿瘤转移/肿瘤细胞系Key words
breast cancer/anoikis/messenger RNA/methylation/apoptosis-modulating proteins/tumor gene expression regulation/tumor metastasis/tumor cell line分类
医药卫生引用本文复制引用
张云姣,张博,汪家佳,张雪,陈曦,凌瑞,张健..BAK1 m6A甲基化修饰在乳腺癌细胞失巢凋亡中的作用和机制研究[J].空军军医大学学报,2025,46(7):900-905,912,7.基金项目
国家自然科学基金(82372960) （82372960）
陕西省创新能力支撑计划项目(2023-CX-TD-67,2022TD-47) （2023-CX-TD-67,2022TD-47）
空军军医大学西京医院学科助推计划项目(XJZT24CY53,XJZT24JC17) （XJZT24CY53,XJZT24JC17）
