ALKBH5去除SCT2的m6A甲基化修饰促进胃癌侵袭的机制研究  

ALKBH5 demethylates m6A modifications in STC2 mRNA and promotes the invasion of gastric cancer

作　　者：曹献馗 谢斌 邵旸 林杰[1] CAO Xiankui;XIE Bin;SHAO Yang;LIN Jie(Department of General Surgery,Liaoning Cancer Hospital,Shenyang 110000,China)

机构地区：[1]辽宁省肿瘤医院普外科,辽宁沈阳110000

出　　处：《胃肠病学和肝病学杂志》2023年第2期176-181,共6页Chinese Journal of Gastroenterology and Hepatology

基　　金：辽宁省自然科学基金(2019-ZD-0592)。

摘　　要：目的 评估AlkB同系物5(AlkB homolog 5,ALKBH5)介导的m6A甲基化修饰对胃癌侵袭的影响,并对其机制进行探讨。方法 RT-PCR检测胃癌细胞中ALKBH5和STC2表达。TCGA分析ALKBH5和STC2表达及相关性。在胃癌细胞中敲降ALKBH5,免疫沉淀检测STC2的m6A甲基化表达变化。在胃癌细胞中抑制ALKBH5表达后,检测STC2的表达;在胃癌细胞中抑制ALKBH5后,再过表达STC2,Transwell和划痕实验评估胃癌细胞侵袭能力变化;Western blotting检测EMT相关分子标志物表达变化。结果 与胃黏膜细胞GES-1相比,胃癌细胞中ALKBH5和STC2均高表达(P<0.05);抑制ALKBH5表达后胃癌细胞中STC2表达随之下降;胃癌细胞中抑制ALKBH5表达后,细胞侵袭能力明显减弱(P<0.05),而在此基础上过表达STC2后侵袭能力部分恢复(P<0.05);ALKBH5和STC2协同影响EMT。结论 ALKBH5可通过调控STC2的表达促进胃癌细胞侵袭。Objective To investigate the role of AlkB homolog 5(ALKBH5)-mediated m6A methylation modifications in gastric cancer cells invasive. Methods The expression of ALKBH5 and STC2 in gastric cancer cells was detected by RT-PCR. TCGA data was used to analysis of ALKBH5 and STC2 expression and correlation. ALKBH5 was knocked down in gastric cancer cells and the change in m6A methylation expression of STC2 was detected by immunoprecipitation. The changes in abilities of invasive and metastasis in gastric cancer cells after ALKBH5 knock-down and overexpressed STC2 were examined by scrape and Transwell assay. The expressions of EMT associated biomarkers were tested by Western blotting. Results The expression levels of both ALKBH5 and STC2 were significantly higher in gastric cancer cells compared with GES-1(P<0.05);ALKBH5 regulated the m6A methylation level of STC2. Transfection with siRNA ALKBH5 down-regulated STC2 expression(P<0.05). In gastric cancer cells, the abilities of invasive was significantly reduced after ALKBH5 knock-down(P<0.05). And the overexpression of STC2 could reverse this phenomenon(P<0.05). In addition, ALKBH5 and STC2 jointly affected the biomarkers of EMT. Conclusion ALKBH5 can promote the invasive of gastric cancer cells by requlating the expression of STC2.

关 键 词：胃癌 ALKBH5 STC2 侵袭 上皮-间质转化 

分 类 号：R735.2[医药卫生—肿瘤]