Xiuqing Dong1,2, Geng Chen1,2,3, Zhixiong Cai1,2,3, Zhenli Li1,2, Liman Qiu1,2, Haipo Xu1,2, Yuan Yuan1,2, Xiao-Long Liu1,2, Jingfeng Liu1,4,2. 1. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. 2. The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China. 3. School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. 4. Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
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.
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.
Authors: Stephin J Vervoort; Jennifer R Devlin; Nicholas Kwiatkowski; Mingxing Teng; Nathanael S Gray; Ricky W Johnstone Journal: Nat Rev Cancer Date: 2021-10-21 Impact factor: 60.716
Authors: Julia Ramírez-Moya; Christos Miliotis; Allison R Baker; Richard I Gregory; Frank J Slack; Pilar Santisteban Journal: Mol Cancer Date: 2021-09-08 Impact factor: 41.444