FTO-mediated m6A demethylation inhibits bladder cancer progression via decreasing EMG1 and reducing ribosome biosynthesis.

Bladder cancer (BLCA) is one of the most common urological malignancies, entailing significant morbidity and mortality rates. A comprehensive understanding of the mechanisms driving bladder cancer initiation and development is required to devise improved treatment regimens. N6-methyladenosine (m6A) is the most prevalent internal RNA modification reported to regulate cancer metastasis. Here, the function of fat mass and obesity-associated protein (FTO), an m6A demethylase, was studied in bladder cancer by overexpressing or knocking down FTO, and the underlying mechanism of FTO in BLCA was explored using machine learning analysis, in vitro, and in vivo experiments. The FTO expression has been proven to be downregulated within bladder cancer, and it could exert a tumor-suppressive effect. Moreover, Gain- and loss-of-function experiments showed that FTO downregulation enhanced the proliferation, migration, and invasion of bladder cancer cells. Mechanistic studies revealed that FTO decreased EMG1 expression by demethylating EMG1 and reducing ribosome biosynthesis, thereby promoting bladder cancer cell proliferation, migration, and invasion and repressing tumor growth in vivo. This study has demonstrated the anti-tumor effect of FTO on bladder cancer development, making it a promising therapeutic target.