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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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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. |
format | Online Article Text |
id | pubmed-10034049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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