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Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer
BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941714/ https://www.ncbi.nlm.nih.gov/pubmed/33750326 http://dx.doi.org/10.1186/s12885-021-07995-2 |
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author | Chen, Jingyi Song, Yuxuan Li, Mei Zhang, Yu Lin, Tingru Sun, Jie Wang, Di Liu, Yulan Guo, Jingzhu Yu, Weidong |
author_facet | Chen, Jingyi Song, Yuxuan Li, Mei Zhang, Yu Lin, Tingru Sun, Jie Wang, Di Liu, Yulan Guo, Jingzhu Yu, Weidong |
author_sort | Chen, Jingyi |
collection | PubMed |
description | BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. METHODS: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. RESULTS: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. CONCLUSIONS: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07995-2. |
format | Online Article Text |
id | pubmed-7941714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79417142021-03-09 Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer Chen, Jingyi Song, Yuxuan Li, Mei Zhang, Yu Lin, Tingru Sun, Jie Wang, Di Liu, Yulan Guo, Jingzhu Yu, Weidong BMC Cancer Research Article BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. METHODS: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. RESULTS: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. CONCLUSIONS: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07995-2. BioMed Central 2021-03-09 /pmc/articles/PMC7941714/ /pubmed/33750326 http://dx.doi.org/10.1186/s12885-021-07995-2 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Chen, Jingyi Song, Yuxuan Li, Mei Zhang, Yu Lin, Tingru Sun, Jie Wang, Di Liu, Yulan Guo, Jingzhu Yu, Weidong Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title | Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title_full | Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title_fullStr | Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title_full_unstemmed | Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title_short | Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer |
title_sort | comprehensive analysis of cerna networks reveals prognostic lncrnas related to immune infiltration in colorectal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941714/ https://www.ncbi.nlm.nih.gov/pubmed/33750326 http://dx.doi.org/10.1186/s12885-021-07995-2 |
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