生物
RNA编辑
核糖核酸
阿达尔
癌症研究
癌变
转录组
抑癌基因
细胞周期
细胞生长
细胞生物学
基因
分子生物学
基因表达
遗传学
作者
Fang-Yi Han,Minxuan Hu,Linjie Zhang,Xingdi Fan,Junrao Wang,Zhengchi Lou,Shuyang Wang,Lijie Chen,Yaping Ye,Yanqing Ding,Hong-Li Jiao
标识
DOI:10.1016/j.yexcr.2022.113209
摘要
The bladder cancer-associated protein (BLCAP) gene is a tumor-suppressor gene as its encoded protein can inhibit cell proliferation by stimulating apoptosis in many malignant tumors. It is also a novel site of adenosine-to-inosine (A-to-I) RNA editing by ADAR (adenosine deaminase acting on RNA). In this study, we found by exome and transcriptome sequencing that there was an abnormal RNA editing event of the BLCAP gene in colorectal cancer (CRC) tissues compared to adjacent normal tissues. The editing of BLCAP transcripts promoted the degradation of BLCAP by ubiquitination, so BLCAP could not maintain its function as a tumor suppressor gene in CRC. Moreover, our further studies revealed that BLCAP could interact with Rb1 and inhibit its phosphorylation, while the loss of repressive effect due to reduced BLCAP protein levels caused by A-to-I RNA editing facilitates the transition from G1 to S phase of the cell cycle, leading to increased cell proliferation and reduced apoptosis. Thus, A-to-I RNA editing events tend to play an essential role in CRC carcinogenesis.
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