METTL16 suppressed the proliferation and cisplatin-chemoresistance of bladder cancer by degrading PMEPA1 mRNA in a m6A manner through autophagy pathway
Hao Yu, Juntao Zhuang, Zijian Zhou, Qiang Song, Jiancheng Lv, Xiao Yang, Haiwei Yang, Qiang Lü
Abstract
. In addition, METTL16 reduced the mRNA stability of prostate transmembrane protein androgen induced-1 (PMEPA1) via binding to its m6A site in the 3'-UTR, thereby inhibited the proliferation of bladder cancer cells and increased the sensitivity of cisplatin through PMEPA1-mediated autophagy pathway. Finally, we found that hypoxia-inducible factor 2α (HIF-2α) exerted its tumor-promoting effect by binding the METTL16 promoter region to repress its transcription. Taken together, High expression of METTL16 predicted better survival in BLCA. METTL16 significantly inhibited bladder cancer cell proliferation and sensitized bladder cancer cells to cisplatin via HIF-2α-METTL16-PMEPA1-autophagy axis in a m6A manner. These findings might provide fresh insights into BLCA therapy.