YTHDF1 Promotes Bladder Cancer Cell Proliferation via the METTL3/YTHDF1-RPN2-PI3K/AKT/mTOR Axis

N6-methyladenosine (m6A) is the most common mRNA modification and it plays a critical role in tumor progression, prognoses and therapeutic response. In recent years, more and more studies have shown that m6A modifications play an important role in bladder carcinogenesis and development. However, the regulatory mechanisms of m6A modifications are complex. Whether the m6A reading protein YTHDF1 is involved in the development of bladder cancer remains to be elucidated. The aims of this study were to determine the association between METTL3/YTHDF1 and bladder cancer cell proliferation and cisplatin resistance to explore the downstream target genes of METTL3/YTHDF1 and to explore the therapeutic implications for bladder cancer patients. The results showed that the reduced expression of METTL3/YTHDF1 could lead to decreased bladder cancer cell proliferation and cisplatin sensitivity. Meanwhile, overexpression of the downstream target gene, RPN2, could rescue the effect of reduced METTL3/YTHDF1 expression on bladder cancer cells. In conclusion, this study proposes a novel METTL3/YTHDF1-RPN2-PI3K/AKT/mTOR regulatory axis that affects bladder cancer cell proliferation and cisplatin sensitivity.

Automated summary

N6-methyladenosine (m6A) is a common mRNA modification that plays a critical role in tumor progression, prognoses, and therapeutic response. This study focuses on the role of m6A modifications in bladder carcinogenesis and development and investigates the association between METTL3/YTHDF1 and bladder cancer cell proliferation and cisplatin resistance. The results show that reduced expression of METTL3/YTHDF1 leads to decreased bladder cancer cell proliferation and cisplatin sensitivity, while overexpression of the downstream target gene, RPN2, can rescue this effect.