Dysregulation of USP18/FTO/PYCR1 signaling network promotes bladder cancer development and progression

被引：43

作者：

Song, Wei ^{[1
]}

Yang, Ke ^{[1
]}

Luo, Jianjun ^{[1
]}

Gao, Zhiyong ^{[1
]}

Gao, Yunliang ^{[2
]}

机构：

[1] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 2, Dept Urol, Changsha 410005, Hunan, Peoples R China

[2] Cent South Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Hunan, Peoples R China

来源：

AGING-US | 2021年 / 13卷 / 03期

关键词：

N6-methyladenosine; m6A; methylation; FTO; bladder cancer; MESSENGER-RNA METHYLATION; PYRROLINE-5-CARBOXYLATE REDUCTASE; NUCLEAR-RNA; WEB SERVER; FTO GENE; FAT MASS; EXPRESSION; OBESITY; DATABASE; PROTEIN;

D O I：

10.18632/aging.202359

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

N6-methyladenosine refers to a methylation of adenosine base at the 6th nitrogen position, which is the dominant methylation modification in both message and non-coding RNAs. Dysregulation of RNA m6A methylation causes tumorigenesis in humans. The key N6-methyladenosine demethylase fat-mass and obesity-associated protein (FTO) is negatively correlated with the overall survival of bladder cancer patients, but the underlying mechanism remains poorly understood. In this study, we demonstrated that the post-translational deubiquitination by USP18 up-regulates the protein but not mRNA of FTO in bladder cancer tissues and cells. As a result, FTO decreased N6-methyladenosine methylation level in PYCR1 through its demethylase enzymatic activity and stabilized PYCR1 transcript to promote bladder cancer initiation and progression. Our work shows the importance of N6-methyladenosine RNA modification in bladder cancer development, and highlights UPS18/FTO/PYCR1 signaling network as potential therapeutic targets of bladder cancer.

引用

页码：3909 / 3925

页数：17

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