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The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer

An abnormality in the regulation of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyzed adenosine-to-inosine (A-to-I) RNA editing, was closely associated with the highly aggressive biologic behavior and poor prognosis in many malignancies. In the present study, we aimed to investigate...

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Autores principales: Zheng, Guo-Liang, Zhang, Guo-Jun, Zhao, Yan, Zheng, Zhi-Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845036/
https://www.ncbi.nlm.nih.gov/pubmed/36660243
http://dx.doi.org/10.1155/2023/9315027
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author Zheng, Guo-Liang
Zhang, Guo-Jun
Zhao, Yan
Zheng, Zhi-Chao
author_facet Zheng, Guo-Liang
Zhang, Guo-Jun
Zhao, Yan
Zheng, Zhi-Chao
author_sort Zheng, Guo-Liang
collection PubMed
description An abnormality in the regulation of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyzed adenosine-to-inosine (A-to-I) RNA editing, was closely associated with the highly aggressive biologic behavior and poor prognosis in many malignancies. In the present study, we aimed to investigate the relationship among transcript factors-microRNAs regulatory network, immune environment, and ADAR gene in colorectal carcinoma (CRC). The association among the expression levels of ADAR mRNA and copy number variation, methylation, and mutation status were comprehensively analyzed using cBioPortal, Wanderer, and UALCAN databases in CRC datasets. ADAR-transcript factors (TFs) and ADAR-miRNA regulation networks were constructed by Cistrome Cancer and miRWalk2.0, respectively. The full network and subnetworks for ADAR coexpression genes were constructed using the STRING database and visualized by the MCODE module of the Cytoscape app. The relationship between ADAR mRNA expression and the abundance of infiltrating immune cells in CRC patients was explored by the Tumor Immune Estimation Resource, CIBERSORT, and single-gene gene set enrichment analysis (GSEA). ADAR mRNA was elevated and was a cancer essential gene in CRC. ADAR mRNA and transcripts P110 were significantly elevated in CRC compared to normal controls. Low-level methylation in the promoter region and high copy number amplification of ADAR were responsible for high levels of ADAR mRNA expression. ADAR coexpression genes were mainly involved in immunoregulation, especially T-lymphocyte activation. Hub genes, including CD2, CD274, and FASLG, were also significantly upregulated in the ADAR-high group compared to the control group. Besides, M1 macrophages were enriched in the ADAR-high group compared to the control group. This study demonstrated that ADAR, a new essential gene, was involved in the immune regulator and was a novel immune treatment target in CRC.
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spelling pubmed-98450362023-01-18 The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer Zheng, Guo-Liang Zhang, Guo-Jun Zhao, Yan Zheng, Zhi-Chao J Oncol Research Article An abnormality in the regulation of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyzed adenosine-to-inosine (A-to-I) RNA editing, was closely associated with the highly aggressive biologic behavior and poor prognosis in many malignancies. In the present study, we aimed to investigate the relationship among transcript factors-microRNAs regulatory network, immune environment, and ADAR gene in colorectal carcinoma (CRC). The association among the expression levels of ADAR mRNA and copy number variation, methylation, and mutation status were comprehensively analyzed using cBioPortal, Wanderer, and UALCAN databases in CRC datasets. ADAR-transcript factors (TFs) and ADAR-miRNA regulation networks were constructed by Cistrome Cancer and miRWalk2.0, respectively. The full network and subnetworks for ADAR coexpression genes were constructed using the STRING database and visualized by the MCODE module of the Cytoscape app. The relationship between ADAR mRNA expression and the abundance of infiltrating immune cells in CRC patients was explored by the Tumor Immune Estimation Resource, CIBERSORT, and single-gene gene set enrichment analysis (GSEA). ADAR mRNA was elevated and was a cancer essential gene in CRC. ADAR mRNA and transcripts P110 were significantly elevated in CRC compared to normal controls. Low-level methylation in the promoter region and high copy number amplification of ADAR were responsible for high levels of ADAR mRNA expression. ADAR coexpression genes were mainly involved in immunoregulation, especially T-lymphocyte activation. Hub genes, including CD2, CD274, and FASLG, were also significantly upregulated in the ADAR-high group compared to the control group. Besides, M1 macrophages were enriched in the ADAR-high group compared to the control group. This study demonstrated that ADAR, a new essential gene, was involved in the immune regulator and was a novel immune treatment target in CRC. Hindawi 2023-01-10 /pmc/articles/PMC9845036/ /pubmed/36660243 http://dx.doi.org/10.1155/2023/9315027 Text en Copyright © 2023 Guo-Liang Zheng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zheng, Guo-Liang
Zhang, Guo-Jun
Zhao, Yan
Zheng, Zhi-Chao
The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title_full The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title_fullStr The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title_full_unstemmed The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title_short The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
title_sort interplay between rna editing regulator adar1 and immune environment in colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845036/
https://www.ncbi.nlm.nih.gov/pubmed/36660243
http://dx.doi.org/10.1155/2023/9315027
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