由ADAR1介导的CDK13 RNA过度编辑与肝细胞癌患者的不良预后相关。

CDK13 RNA Over-Editing Mediated by ADAR1 Associates with Poor Prognosis of Hepatocellular Carcinoma Patients.

作者信息

Dong Xiuqing, Chen Geng, Cai Zhixiong, Li Zhenli, Qiu Liman, Xu Haipo, Yuan Yuan, Liu Xiao-Long, Liu Jingfeng

机构信息

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.

The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China.

出版信息

Cell Physiol Biochem. 2018;47(6):2602-2612. doi: 10.1159/000491656. Epub 2018 Jul 11.

DOI:10.1159/000491656

PMID:29996118

Abstract

BACKGROUND/AIMS: Aberrant RNA editing, mediated by adenosine deaminases acting on RNA (ADAR), serves as a post-transcriptional event participating in tumorigenesis and prognosis. However, the RNA editing profiles during HCC progression and their clinical correlations remain unclear.

METHODS

Multiple tissue samples were collected from an advanced HCC patient. RNA-seq was performed to obtain the RNA editing profiles for each sample. Two RNA editing sites from CDK13 were further validated in 60 HCC patients; and their potential regulatory mechanisms were investigated.

RESULTS

In-depth analysis of the RNA-seq data revealed a significant number of editing sites (632-816) in coding regions for each tissue sample, showing branched evolution during tumorigenesis and metastasis. Two editing sites (Q103R and K96R) in CDK13 showed significant over-editing in tumor, and these phenomenon were validated in 60 HCC patients. Furthermore, the clinicopathological analysis revealed that these CDK13 over-editing sites were positively associated with TNM, PVTT and poor prognosis. In addition, the editing level of these sites were significantly correlated with the expression of ADAR1. Loss of function assays further proved that these CDK13 over-editing sites were mediated by ADAR1 in HCC cells.

CONCLUSIONS

CDK13 RNA over-editing sites mediated by ADAR1 may serve as novel cancer driver events in HCC progression.

摘要

背景/目的：由作用于RNA的腺苷脱氨酶（ADAR）介导的异常RNA编辑是一种参与肿瘤发生和预后的转录后事件。然而，肝癌进展过程中的RNA编辑谱及其临床相关性仍不清楚。

方法

从一名晚期肝癌患者收集多个组织样本。进行RNA测序以获得每个样本的RNA编辑谱。在60例肝癌患者中进一步验证了来自CDK13的两个RNA编辑位点；并研究了它们潜在的调控机制。

结果

对RNA测序数据的深入分析揭示了每个组织样本编码区中有大量编辑位点（632 - 816个），显示出在肿瘤发生和转移过程中的分支进化。CDK13中的两个编辑位点（Q103R和K96R）在肿瘤中显示出显著的过度编辑，并且这些现象在60例肝癌患者中得到验证。此外，临床病理分析显示，这些CDK13过度编辑位点与TNM、门静脉癌栓和不良预后呈正相关。另外，这些位点的编辑水平与ADAR1的表达显著相关。功能丧失实验进一步证明，这些CDK13过度编辑位点在肝癌细胞中由ADAR1介导。