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Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment

RNA editing is prevalent in the transcriptome and is important for multiple cellular processes. C-to-U RNA editing sites (RES) are relatively rare and understudied in humans, compared to A-to-I editing. However, the functional impact of C-to-U editing in human cancers also remains elusive. Here, we...

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Autores principales: Guo, Mengbiao, Li, Feng, Zhao, Linghao, Fang, Zhengwen, Yu, Huichuan, Songyang, Zhou, Xiong, Yuanyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034049/
https://www.ncbi.nlm.nih.gov/pubmed/36969056
http://dx.doi.org/10.3389/fonc.2023.1097667
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author Guo, Mengbiao
Li, Feng
Zhao, Linghao
Fang, Zhengwen
Yu, Huichuan
Songyang, Zhou
Xiong, Yuanyan
author_facet Guo, Mengbiao
Li, Feng
Zhao, Linghao
Fang, Zhengwen
Yu, Huichuan
Songyang, Zhou
Xiong, Yuanyan
author_sort Guo, Mengbiao
collection PubMed
description RNA editing is prevalent in the transcriptome and is important for multiple cellular processes. C-to-U RNA editing sites (RES) are relatively rare and understudied in humans, compared to A-to-I editing. However, the functional impact of C-to-U editing in human cancers also remains elusive. Here, we conducted the first comprehensive survey of pan-cancer C-to-U RESs. Surprisingly, we found that the same subset of RESs were associated with multiple features, including patient survival, cancer stemness, tumor mutation burden (TMB), and tumor-infiltrated immune cell compositions (ICC), suggesting an RES-mediated close relationship between these features. For example, editing sites for GALM or IFI6 that led to higher expression were linked to lower survival and more cancer stemness. Also, TMB was found to be lower in prostate cancer cases with ICC-associated RESs in CAVIN1 or VWA8 or higher in prostate cancer cases with thymoma. With experimental support, we also found RESs in CST3, TPI1, or TNC that are linked to immune checkpoint blockade by anti-PD1. We also confirmed through experiments that two C-to-U RESs in CSNK2B or RPS14 had different effects on colon cancer cells. Patients with CSNK2B editing, which increased the expression of the oncogene CLDN18, had a lower response to drugs. On the other hand, drugs worked better on people who had RPS14 editing, which greatly increased ribosome production. In summary, our study demonstrated the important roles of C-to-U RESs across cancers and shed light on personalized cancer therapy.
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spelling pubmed-100340492023-03-24 Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment Guo, Mengbiao Li, Feng Zhao, Linghao Fang, Zhengwen Yu, Huichuan Songyang, Zhou Xiong, Yuanyan Front Oncol Oncology RNA editing is prevalent in the transcriptome and is important for multiple cellular processes. C-to-U RNA editing sites (RES) are relatively rare and understudied in humans, compared to A-to-I editing. However, the functional impact of C-to-U editing in human cancers also remains elusive. Here, we conducted the first comprehensive survey of pan-cancer C-to-U RESs. Surprisingly, we found that the same subset of RESs were associated with multiple features, including patient survival, cancer stemness, tumor mutation burden (TMB), and tumor-infiltrated immune cell compositions (ICC), suggesting an RES-mediated close relationship between these features. For example, editing sites for GALM or IFI6 that led to higher expression were linked to lower survival and more cancer stemness. Also, TMB was found to be lower in prostate cancer cases with ICC-associated RESs in CAVIN1 or VWA8 or higher in prostate cancer cases with thymoma. With experimental support, we also found RESs in CST3, TPI1, or TNC that are linked to immune checkpoint blockade by anti-PD1. We also confirmed through experiments that two C-to-U RESs in CSNK2B or RPS14 had different effects on colon cancer cells. Patients with CSNK2B editing, which increased the expression of the oncogene CLDN18, had a lower response to drugs. On the other hand, drugs worked better on people who had RPS14 editing, which greatly increased ribosome production. In summary, our study demonstrated the important roles of C-to-U RESs across cancers and shed light on personalized cancer therapy. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034049/ /pubmed/36969056 http://dx.doi.org/10.3389/fonc.2023.1097667 Text en Copyright © 2023 Guo, Li, Zhao, Fang, Yu, Songyang and Xiong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Guo, Mengbiao
Li, Feng
Zhao, Linghao
Fang, Zhengwen
Yu, Huichuan
Songyang, Zhou
Xiong, Yuanyan
Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title_full Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title_fullStr Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title_full_unstemmed Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title_short Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment
title_sort pan-cancer investigation of c-to-u editing reveals its important role in cancer development and new targets for cancer treatment
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034049/
https://www.ncbi.nlm.nih.gov/pubmed/36969056
http://dx.doi.org/10.3389/fonc.2023.1097667
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