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Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma

BACKGROUND: Microsatellite instability-high (MSI-H) is a special type of human colon adenocarcinoma (COAD) that responds well to immunotherapy. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are important members of competing endogenous RNAs (ceRNAs) networks, are involved in the tumor...

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Autores principales: Li, Changhao, Zhu, Zhenyu, Hou, Qingsheng, Wang, Bishi, Zou, Lei, Liu, Luguang, Gong, Weipeng, Guo, Hongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799078/
https://www.ncbi.nlm.nih.gov/pubmed/35116380
http://dx.doi.org/10.21037/tcr-21-2380
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author Li, Changhao
Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Zou, Lei
Liu, Luguang
Gong, Weipeng
Guo, Hongliang
author_facet Li, Changhao
Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Zou, Lei
Liu, Luguang
Gong, Weipeng
Guo, Hongliang
author_sort Li, Changhao
collection PubMed
description BACKGROUND: Microsatellite instability-high (MSI-H) is a special type of human colon adenocarcinoma (COAD) that responds well to immunotherapy. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are important members of competing endogenous RNAs (ceRNAs) networks, are involved in the tumorigenesis and development of MSI-H COAD. This study aimed to establish a ceRNA network for MSI in COAD to identify targets and prognostic markers that may explain the effects of immunotherapy. METHODS: COAD sequencing data were extracted from The Cancer Genome Atlas (TCGA), after which differentially expressed miRNAs, lncRNAs, and mRNAs were determined according to microsatellite status. After building a network based on the ceRNA hypothesis, the relationships between microsatellite status and clinical features were explored. Biological processes in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were analyzed for specific miRNAs, lncRNAs, and mRNAs. Survival analysis was used to identify potential biomarkers. RESULTS: Based on the inclusion criteria, a total of 363 COAD samples were obtained from TCGA. Strict screening criteria were used to identify differentially expressed RNAs in the MSI-H and microsatellite-stable groups, with 82 miRNAs, 1,280 lncRNAs, and 2121 mRNAs obtained (fold change >2, false discovery rate <0.01). Based on the RNA interaction mechanism, a miRNA-lncRNA-mRNA network was constructed, through which a subnetwork composed of 5 miRNAs was discovered. hsa-miR-31-5p, hsa-miR-302a-3p, hsa-miR-302b-3p, hsa-miR-302d-3p, hsa-miR-3619-5p and the RNAs interaction with them have the potential to become novel targets to change the effect of existing immunotherapy. GO and KEGG analyses showed that these differentially expressed miRNAs, lncRNAs, and mRNAs may play key roles in tumorigenesis, tumor development, and drug efficacy, with natural killer cells potentially becoming the next emerging targets for immunotherapy enhancement. Moreover, survival analysis identified 10 lncRNAs as potential survival markers. CONCLUSIONS: This study identified novel immunotherapy targets and revealed potential biomarkers for COAD according to microsatellite status.
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spelling pubmed-87990782022-02-02 Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma Li, Changhao Zhu, Zhenyu Hou, Qingsheng Wang, Bishi Zou, Lei Liu, Luguang Gong, Weipeng Guo, Hongliang Transl Cancer Res Original Article BACKGROUND: Microsatellite instability-high (MSI-H) is a special type of human colon adenocarcinoma (COAD) that responds well to immunotherapy. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are important members of competing endogenous RNAs (ceRNAs) networks, are involved in the tumorigenesis and development of MSI-H COAD. This study aimed to establish a ceRNA network for MSI in COAD to identify targets and prognostic markers that may explain the effects of immunotherapy. METHODS: COAD sequencing data were extracted from The Cancer Genome Atlas (TCGA), after which differentially expressed miRNAs, lncRNAs, and mRNAs were determined according to microsatellite status. After building a network based on the ceRNA hypothesis, the relationships between microsatellite status and clinical features were explored. Biological processes in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were analyzed for specific miRNAs, lncRNAs, and mRNAs. Survival analysis was used to identify potential biomarkers. RESULTS: Based on the inclusion criteria, a total of 363 COAD samples were obtained from TCGA. Strict screening criteria were used to identify differentially expressed RNAs in the MSI-H and microsatellite-stable groups, with 82 miRNAs, 1,280 lncRNAs, and 2121 mRNAs obtained (fold change >2, false discovery rate <0.01). Based on the RNA interaction mechanism, a miRNA-lncRNA-mRNA network was constructed, through which a subnetwork composed of 5 miRNAs was discovered. hsa-miR-31-5p, hsa-miR-302a-3p, hsa-miR-302b-3p, hsa-miR-302d-3p, hsa-miR-3619-5p and the RNAs interaction with them have the potential to become novel targets to change the effect of existing immunotherapy. GO and KEGG analyses showed that these differentially expressed miRNAs, lncRNAs, and mRNAs may play key roles in tumorigenesis, tumor development, and drug efficacy, with natural killer cells potentially becoming the next emerging targets for immunotherapy enhancement. Moreover, survival analysis identified 10 lncRNAs as potential survival markers. CONCLUSIONS: This study identified novel immunotherapy targets and revealed potential biomarkers for COAD according to microsatellite status. AME Publishing Company 2021-12 /pmc/articles/PMC8799078/ /pubmed/35116380 http://dx.doi.org/10.21037/tcr-21-2380 Text en 2021 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Li, Changhao
Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Zou, Lei
Liu, Luguang
Gong, Weipeng
Guo, Hongliang
Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title_full Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title_fullStr Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title_full_unstemmed Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title_short Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
title_sort revealing potential immunotherapy targets through analysis of a cerna network in human colon adenocarcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799078/
https://www.ncbi.nlm.nih.gov/pubmed/35116380
http://dx.doi.org/10.21037/tcr-21-2380
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