膀胱癌
癌症研究
免疫疗法
免疫系统
基因敲除
阿替唑单抗
N6-甲基腺苷
肿瘤微环境
癌症
癌基因
甲基化
医学
癌症免疫疗法
细胞
生物
细胞周期
细胞凋亡
免疫学
内科学
甲基转移酶
基因
彭布罗利珠单抗
生物化学
遗传学
作者
Hongyu Deng,Faqing Tang,Ming Zhou,Dongyong Shan,Xingyu Chen,Ke Cao
标识
DOI:10.3389/fonc.2022.820242
摘要
N6-methyladenosine (m6A) has emerged as one of the most important modifications of RNA. Based on the expression of 23 different modes of m6A regulatory factors, we identified three different m6A modification patterns in bladder cancer. The effects of the three different modes of m6A modification on clinicopathological characteristics, immune cell infiltration levels and expression levels of immune checkpoint genes were comprehensively analyzed. In addition, the effects of different modes of m6A modification on the therapeutic efficacy of anti-PD-L1 immunotherapy (atezolizumab) are also discussed. Our results confirm that m6A methylation plays an important role in immune cell recruitment in the tumor microenvironment of bladder cancer, which influences the efficacy of anti-PD-L1 therapy for bladder cancer. We further confirmed the important role of FTO protein in the biological function of bladder cancer cells by performing in vitro experiments. FTO functions as an oncogene in bladder cancer cells, and upon FTO knockdown, the level of m6A enzyme activity in bladder cancer cells was significantly increased, apoptosis was increased, and cell proliferation and cell invasion were reduced. In addition, our study also confirmed that K216H and K216E are probably important targets for regulating FTO. We provide new insights into the regulatory pathways of the immune microenvironment and the methylation function of m6A in bladder cancer, which will help in designing novel diagnostic methods, prognostic tools, and therapeutic targets.
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