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Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer

Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new...

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Autores principales: Sheng, Han, Pan, Huan, Yao, Ming, Xu, Longsheng, Lu, Jianju, Liu, Beibei, Shen, Jianfen, Shen, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712159/
https://www.ncbi.nlm.nih.gov/pubmed/34966440
http://dx.doi.org/10.1155/2021/1732176
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author Sheng, Han
Pan, Huan
Yao, Ming
Xu, Longsheng
Lu, Jianju
Liu, Beibei
Shen, Jianfen
Shen, Hui
author_facet Sheng, Han
Pan, Huan
Yao, Ming
Xu, Longsheng
Lu, Jianju
Liu, Beibei
Shen, Jianfen
Shen, Hui
author_sort Sheng, Han
collection PubMed
description Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA–miRNA pairs and miRNA–mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA–miRNA pairs and 140 miRNA–mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA–mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.
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spelling pubmed-87121592021-12-28 Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer Sheng, Han Pan, Huan Yao, Ming Xu, Longsheng Lu, Jianju Liu, Beibei Shen, Jianfen Shen, Hui Comput Math Methods Med Research Article Circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. Yet, the roles of cancer-specific circRNAs in the circRNA-related ceRNA network of breast cancer (BRCA) remain unclear. The aim of this study was to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer. We downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA–miRNA pairs and miRNA–mRNA pairs. Gene ontology and pathway enrichment analyses were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. A total of 72 DEcircRNAs, 158 DEmiRNAs, and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA–miRNA pairs and 140 miRNA–mRNA pairs, including 40 circRNAs, 30 miRNAs, and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in the PI3K-Akt signaling pathway, microRNAs in cancer, and proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA–mRNA interaction pairs had a significant negative correlation. A PPI network was established, and 21 hub genes were determined from the network. This study provides an effective bioinformatics basis for further understanding of the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis. Hindawi 2021-12-20 /pmc/articles/PMC8712159/ /pubmed/34966440 http://dx.doi.org/10.1155/2021/1732176 Text en Copyright © 2021 Han Sheng 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
Sheng, Han
Pan, Huan
Yao, Ming
Xu, Longsheng
Lu, Jianju
Liu, Beibei
Shen, Jianfen
Shen, Hui
Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title_full Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title_fullStr Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title_full_unstemmed Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title_short Integrated Analysis of Circular RNA-Associated ceRNA Network Reveals Potential circRNA Biomarkers in Human Breast Cancer
title_sort integrated analysis of circular rna-associated cerna network reveals potential circrna biomarkers in human breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712159/
https://www.ncbi.nlm.nih.gov/pubmed/34966440
http://dx.doi.org/10.1155/2021/1732176
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