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Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma

BACKGROUND: More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional rol...

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Autores principales: Gao, Lei, Zhang, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299662/
https://www.ncbi.nlm.nih.gov/pubmed/34301211
http://dx.doi.org/10.1186/s12885-021-08462-8
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author Gao, Lei
Zhang, Ling
author_facet Gao, Lei
Zhang, Ling
author_sort Gao, Lei
collection PubMed
description BACKGROUND: More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis. METHODS: In this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA–miRNA–mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan–Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD. RESULTS: As a result, 10 circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC. CONCLUSIONS: In summary, a ceRNA network of hsa_circ_0049271 was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11RA, IL7R and MAOA) were remarkably associated with the prognosis of LUAD patients. Among seven mRNA species, four genes (PDGFB, CCND2, CTF1, and IL7R) could be considered as drug targets in LUAD. Our research will provide new insights into the prognosis-related ceRNA network in LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08462-8.
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spelling pubmed-82996622021-07-28 Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma Gao, Lei Zhang, Ling BMC Cancer Research BACKGROUND: More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis. METHODS: In this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA–miRNA–mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan–Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD. RESULTS: As a result, 10 circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC. CONCLUSIONS: In summary, a ceRNA network of hsa_circ_0049271 was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11RA, IL7R and MAOA) were remarkably associated with the prognosis of LUAD patients. Among seven mRNA species, four genes (PDGFB, CCND2, CTF1, and IL7R) could be considered as drug targets in LUAD. Our research will provide new insights into the prognosis-related ceRNA network in LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08462-8. BioMed Central 2021-07-23 /pmc/articles/PMC8299662/ /pubmed/34301211 http://dx.doi.org/10.1186/s12885-021-08462-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Gao, Lei
Zhang, Ling
Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title_full Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title_fullStr Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title_full_unstemmed Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title_short Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma
title_sort construction and comprehensive analysis of a cerna network to reveal potential prognostic biomarkers for lung adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299662/
https://www.ncbi.nlm.nih.gov/pubmed/34301211
http://dx.doi.org/10.1186/s12885-021-08462-8
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