p53蛋白乳酸化促进结肠癌细胞增殖和转移  

p53 lactylation promotes the proliferation and metastasis of colon cancer cells

作　　者：戴瑶 戴海燕 笪文信 王雅卉 张子琦 王胜军 马洁[1] DAI Yao;DAI Haiyan;DA Wenxin;WANG Yahui;ZHANG Ziqi;WANG Shengjun;MA Jie(School of Medicine,Jiangsu University,Zhenjiang Jiangsu 212013;Clinical Laboratory,The Fourth Affiliated People′s Hospital of Jiangsu University,Zhenjiang Jiangsu 212001,China)

机构地区：[1]江苏大学医学院,江苏镇江212013 [2]江苏大学附属第四人民医院检验科,江苏镇江212001

出　　处：《江苏大学学报（医学版）》2023年第4期303-309,共7页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金面上项目(32270964);江苏省重点研发计划社会发展项目(BE2022779);镇江市重点研发计划(社会发展)项目(SH2021027);江苏大学临床医学科技发展基金(JLY2021149)。

摘　　要：目的:探讨p53蛋白乳酸化修饰对结肠癌细胞增殖、转移的影响及其机制。方法:收集人结肠癌组织和相应癌旁组织,经HE染色确认病理形态后,通过乳酸测定试剂盒检测组织与结肠癌细胞HCT116乳酸浓度,免疫组织化学染色法检测组织乳酸化水平和p53表达水平。免疫荧光染色法观察结肠癌组织中的乳酸化和p53蛋白定位,免疫共沉淀检测组织与HCT116细胞中p53蛋白的乳酸化水平。蛋白印迹法检测HCT116细胞中p53蛋白的亚细胞定位。在内源性乳酸介导HCT116细胞的p53蛋白乳酸化修饰以及乳酸抑制剂草氨酸钠抑制p53蛋白乳酸化修饰后,采用CCK-8法检测HCT116细胞的增殖能力,划痕实验和Transwell法检测HCT116细胞的迁移和侵袭能力。结果:人结肠癌组织中乳酸化水平和p53表达水平均高于癌旁组织,并且存在明显的p53蛋白乳酸化修饰。内源性乳酸介导HCT116细胞中p53蛋白乳酸化修饰后,在抑制p53入核的同时促进细胞的增殖、侵袭和迁移。结论:乳酸化p53蛋白通过抑制p53的入核促进结肠癌细胞的增殖和转移。Objective:To investigate the effect and mechanism of p53 lactylation on the proliferation and metastasis of colon cancer cells.Methods:Human colon cancer tissues and corresponding adjacent normal tissues were collected,and the pathological morphology was confirmed by hematoxylin-eosin staining.Lactate concentration was detected by lactate detection kit,and the expression of lactylation and p53 were detected by immunohistochemical staining.The subcellular localization of lactylation and p53 in HCT116 cells were observed by immunofluorescence,and p53 lactylation was detected by immunocoprecipitation.Subsequently,endogenous lactate was used to mediate p53 lactylation of HCT116 cells and the lactate inhibitor oxamate was used to inhibit p53 lactylation.The proliferation ability of HCT116 cells was detected by CCK-8.The migration and invasion ability of HCT116 cells were detected by scratch and Transwell assay.Results:The expression of lactylation and p53 in human colon cancer tissue was higher than that in adjacent normal colon cancer tissue,and p53 lactylation was clearly observed.Endogenous lactate in HCT116 cells can mediate p53 lactylation,inhibit p53 entry into the nucleus,and promote cell proliferation,migration and invasion.Conclusion:p53 lactylation promotes proliferation and metastasis of colon cancer cells by inhibiting the nuclear translocation of p53.

关 键 词：乳酸化修饰 P53蛋白 结肠癌 增殖 转移 

分 类 号：R735[医药卫生—肿瘤] R34[医药卫生—临床医学]