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Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer
Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393335/ https://www.ncbi.nlm.nih.gov/pubmed/36003333 http://dx.doi.org/10.3389/fgene.2022.945414 |
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author | Lu, Can Zhang, Xiaopeng Luo, Yang Huang, Jingang Yu, Minhao |
author_facet | Lu, Can Zhang, Xiaopeng Luo, Yang Huang, Jingang Yu, Minhao |
author_sort | Lu, Can |
collection | PubMed |
description | Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein–protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apc ( min/+ ) and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes. Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK–STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC. Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC. |
format | Online Article Text |
id | pubmed-9393335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93933352022-08-23 Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer Lu, Can Zhang, Xiaopeng Luo, Yang Huang, Jingang Yu, Minhao Front Genet Genetics Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein–protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apc ( min/+ ) and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes. Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK–STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC. Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9393335/ /pubmed/36003333 http://dx.doi.org/10.3389/fgene.2022.945414 Text en Copyright © 2022 Lu, Zhang, Luo, Huang and Yu. 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 | Genetics Lu, Can Zhang, Xiaopeng Luo, Yang Huang, Jingang Yu, Minhao Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title_full | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title_fullStr | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title_full_unstemmed | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title_short | Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer |
title_sort | identification of cxcl10 and cxcl11 as the candidate genes involving the development of colitis-associated colorectal cancer |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393335/ https://www.ncbi.nlm.nih.gov/pubmed/36003333 http://dx.doi.org/10.3389/fgene.2022.945414 |
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