前列腺癌
癌症研究
上皮-间质转换
转移
生物
肿瘤进展
细胞生长
核糖核酸
PI3K/AKT/mTOR通路
蛋白激酶B
癌症
信号转导
细胞生物学
基因
生物化学
遗传学
作者
Jingui Duan,Daogui Fan,Pingping Chen,Jie Xiang,Xin Xie,Yu‐Hui Peng,Jingdi Bai,Tao Li,Yi fan Li,Hui Song,Wenli Fu,Shouxin Zhang,Yan Xiao,Xiaolan Qi,Wei Hong,Jing Zhou,Yan He,ChangXue Wu,Hongmei Zeng,Hua Bai,Tengxiang Chen,Wenfeng Yu,Qifang Zhang
摘要
RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.
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