N6-甲基腺苷（m6A）是哺乳动物mRNAs中最常见的内部修饰。最近的研究表明，m6A甲基转移酶METTL3和METTL14在膀胱癌（BLCA）中发挥重要作用。然而，关键的m6A读取器YTHDF2的影响尚未得到调查。在这里，我们发现在膀胱癌中，YTHDF2在RNA和蛋白质水平都经常上调。功能上，YTHDF2在BLCA细胞的增殖和肿瘤生长中都具有促进作用。整合RNA测序和m6A测序分析显示，RIG-I是YTHDF2的下游靶点。在机制上，YTHDF2结合到DDX58 mRNA的编码序列中，并以m6A依赖的方式介导其降解。RIG-I的敲除抑制凋亡并促进BLCA细胞的增殖。耗竭DDX58也恢复了YTHDF2缺陷所消除的表型。此外，膀胱癌Ythdf2缺陷细胞植入原位会激活先天免疫反应并促进CD8 + T淋巴细胞进入肿瘤床和尿道上皮。因此，针对YTHDF2可能有益于巴氏卡介苗（BCG）免疫治疗。我们的研究揭示了在BLCA中YTHDF2作为一个癌基因，RIG-I作为肿瘤抑制因子。这些发现突出了m6A修饰在BLCA中的功能重要性，并将YTHDF2暗示为BLCA治疗的一个潜在治疗靶点。

N6-Methyladenosine (m6A) is the most prevalent internal modification among mammalian mRNAs. Recent studies show that m6A methyltransferases, METTL3 and METTL14, play important roles in bladder carcinoma (BLCA). However, the impact of YTHDF2, a crucial m6A reader, has yet to be investigated. Here, we found that YTHDF2 is frequently up-regulated at both the RNA and protein level in bladder cancers. Functionally, YTHDF2 promotes the proliferation and tumor growth of BLCA cells in vitro and in vivo, respectively. Integrative RNA-sequencing and m6A-sequencing analyses show that RIG-I is a downstream target of YTHDF2. Mechanistically, YTHDF2 binds to the coding sequence of DDX58 mRNA and mediates its degradation in an m6A-dependent manner. Knock-down of RIG-I inhibits apoptosis and promotes the proliferation of BLCA cells. Depleting DDX58 also restores the phenotype abrogated by YTHDF2 deficiency. Moreover, bladder cancer Ythdf2-deficient cells implanted orthotopically activate an innate immune response and promote the recruitment of CD8+ T lymphocytes into the tumor bed and the urothelium. Consequently, targeting YTHDF2 may be beneficial in Bacillus Calmette-Guérin (BCG) immunotherapy. Our study reveals that YTHDF2 acts as an oncogene and RIG-I as a tumor suppressor in BLCA. These findings highlight the functional importance of the m6A modification in BLCA and implicate YTHDF2 as a potential therapeutic target of BLCA treatment.