丝氨酸
生物合成
结直肠癌
生物
体内
生物化学
氨基酸
甘氨酸
癌症
癌症研究
基因
酶
遗传学
作者
Ning Zhao,Yinghao Cao,Ruikang Tao,Xiuxian Zhu,Runze Li,Y. Chen,Kaixiong Tao,Lei Li,Hengyu Chen,Xianxiong Ma
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-04-18
标识
DOI:10.1158/0008-5472.can-23-2940
摘要
Abstract Circular RNAs (circRNAs) are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circRNA. Here, we found that circMYBL2 in colorectal cancer (CRC) encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of CRC cells in vitro and in vivo. Mechanistically, p185 counteracted UCHL3-mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis. These data revealed that the circMYBL2-encoded p185 isoform serves as a tumor suppressor to inhibit the progression of CRC by reducing serine biosynthesis.
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