FTO调控HOXB13的m6A甲基化修饰促进黑色素瘤侵袭与增殖  

Methylation modification of m6A of HOXB13 in promotion of cutaneous malignant melanoma invasion and proliferation

作　　者：李银玲[1] 表贞淑[1] LI Yin-ling;BIAO Zhen-shu(Department of Dermatology,The People's Hospital of Liaoning Province,Shenyang 110016,China)

机构地区：[1]辽宁省人民医院皮肤科,辽宁沈阳110016

出　　处：《中国美容整形外科杂志》2021年第8期491-495,F0003,共6页Chinese Journal of Aesthetic and Plastic Surgery

摘　　要：目的探讨脂肪肥胖相关蛋白(obesity-associated protein,FTO)和人同源盒蛋白HOXB13(homeobox B13,HOXB13)在皮肤黑色素瘤(cutaneous malignant melanoma,CMM)侵袭和增殖中的作用。方法自2019年1月至2020年12月,辽宁省人民医院皮肤科通过RT-PCR检测CMM细胞FTO和HOXB13表达,TCGA分析FTO和HOXB13表达及相关性,免疫沉淀检测HOXB13的6-甲基腺嘌呤(n6-methyladenosine,m6A)表达变化,CCK-8和Transwell分析FTO和HOXB13在CMM细胞增殖和侵袭中的生物学作用。结果与正常人表皮黑色素细胞相比,CMM细胞中FTO和HOXB13的表达水平均明显升高(P<0.05);FTO调控HOXB13的m6A甲基化水平。CMM中细胞敲降FTO后细胞增殖和侵袭能力明显减弱(P<0.05),而过表达HOXB13后增殖和侵袭能力明显恢复(P<0.05);FTO对CMM恶性表型的影响是通过HOXB13实现的。结论FTO可通过去除HOXB13的m6A甲基化修饰,上调HOXB13的表达促进CMM细胞的增殖和侵袭。Objective To explore the effect of obesity-associated protein(FTO)and human homeobox protein 13(HOXB13)in cutaneous malignant melanoma(CMM)invasion and proliferation.Methods From January 2019 to December 2020,the expression of FTO and HOXB13 in CMM cells was detected by real-time polymerase chain reaction(RT-PCR).The expression and correlation of FTO and HOXB13 was analyzed by TCGA.The changes in expressionof n6-methyladenosine(m6A)of HOXB13 were detected by immunoprecipitation.The biological effects of FTO and HOXB13 on CMM cells proliferation and invasion was analyzed by CCK-8 and Transwell.Results Compared with normal cutaneous malignant melanoma,the expression level of FTO and HOXB13 in CMM cells was significantly increased(P<0.05).The methylation level of m6A of HOXB13 was regulated by FTO.After knocking down FTO in CMM cells,the proliferation and invasion ability was significantly reduced(P<0.05).After overexpression of HOXB13,the proliferation and invasion ability was significantly restored(P<0.05).The effect of FTO on malignant phenotype of CMM was achieved through HOXB13.Conclusion FTO can promote the proliferation and invasion of CMM cells by removing methylation modification of m6A of HOXB13 and up-regulating the expression of HOXB13.

关 键 词：皮肤黑色素瘤 肥胖相关蛋白 人同源盒蛋白HOXB13 m6A甲基化 增殖 侵袭 

分 类 号：R739.5[医药卫生—肿瘤]