A-to-I RNA editing of BLCAP promotes cell proliferation by losing the inhibitory of Rb1 in colorectal cancer
A-to-I RNA editing of BLCAP promotes cell proliferation by losing the inhibitory of Rb1 in colorectal cancer
复制标题
BLCAP 的 A-to-I RNA 编辑通过失去结直肠癌中 Rb1 的抑制来促进细胞增殖
DOI：
10.1016/j.yexcr.2022.113209
复制
发表时间：
2022-05-25
影响因子：
3.7
通讯作者：
Jiao, Hongli
中科院分区：
文献类型：
--
作者：
Han, Fangyi;Hu, Minxuan;Jiao, Hongli
膀胱癌相关蛋白(BLCAP)基因是一种肿瘤抑制基因，其编码的蛋白可通过刺激多种恶性肿瘤细胞的凋亡来抑制细胞增殖。它也是ADAR(作用于RNA的腺苷脱氨酶)编辑腺苷到肌苷(A-to-I)RNA的新位点。本研究通过外显子组和转录组测序发现，结直肠癌组织中存在BLCAP基因的异常RNA编辑事件。BLCAP转录本的编辑通过泛素化促进了BLCAP的降解，因此BLCAP不能维持其作为肿瘤抑制基因在结直肠癌中的功能。此外，我们的进一步研究表明，BLCAP可以与Rb1相互作用并抑制其磷酸化，而A-to-IRNA编辑导致BLCAP蛋白水平降低导致抑制作用的丧失，促进了细胞周期从G1期向S期的过渡，导致细胞增殖增加，细胞凋亡减少。因此，A-to-I RNA编辑事件往往在结直肠癌的发生过程中发挥重要作用。
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 adenosineto-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.