BLCAP 的 A-to-I RNA 编辑通过失去 Rb1 对结直肠癌细胞增殖的抑制作用。

A-to-I RNA editing of BLCAP promotes cell proliferation by losing the inhibitory of Rb1 in colorectal cancer.

机构信息

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.

Laboratory X, Institute X, Department X, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

出版信息

Exp Cell Res. 2022 Aug 15;417(2):113209. doi: 10.1016/j.yexcr.2022.113209. Epub 2022 May 20.

DOI:10.1016/j.yexcr.2022.113209

PMID:35605649

Abstract

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.

摘要

膀胱癌相关蛋白（BLCAP）基因是一种肿瘤抑制基因，其编码的蛋白可以通过刺激许多恶性肿瘤中的细胞凋亡来抑制细胞增殖。它也是 ADAR（腺苷脱氨酶作用于 RNA）介导的腺嘌呤到肌苷（A-to-I）RNA 编辑的新位点。在这项研究中，我们通过外显子组和转录组测序发现，与相邻正常组织相比，结直肠癌（CRC）组织中存在 BLCAP 基因的异常 RNA 编辑事件。BLCAP 转录物的编辑通过泛素化促进 BLCAP 的降解，因此 BLCAP 无法在 CRC 中维持其作为肿瘤抑制基因的功能。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，而由于 A-to-I RNA 编辑导致 BLCAP 蛋白水平降低而丧失抑制作用，促进了细胞周期从 G1 期向 S 期的转变，导致细胞增殖增加和凋亡减少。因此，A-to-I RNA 编辑事件可能在 CRC 的发生中发挥重要作用。