Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease

Background. Accumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associat...

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Main Authors: Jia Mao, Yufei Zhou, Licheng Lu, Ping Zhang, Runhua Ren, Yaqiong Wang, Jing Wang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Cardiology Research and Practice
Online Access:http://dx.doi.org/10.1155/2021/6682183
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author Jia Mao
Yufei Zhou
Licheng Lu
Ping Zhang
Runhua Ren
Yaqiong Wang
Jing Wang
author_facet Jia Mao
Yufei Zhou
Licheng Lu
Ping Zhang
Runhua Ren
Yaqiong Wang
Jing Wang
author_sort Jia Mao
collection DOAJ
description Background. Accumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associated ceRNA networks in CHD. Methods. Data from 6 CHD patients and 32 normal controls were downloaded from the ExoRBase database. CHD and normal controls were compared by screening differentially expressed mRNAs (DEMs), lncRNAs (DELs), and circRNAs (DECs) in serum exosomes. MicroRNAs (miRNAs) targeting DEMs were predicted using the Targetscan and miRanda databases, and miRNAs targeted by DELs and DECs were predicted using the miRcode and starBase databases, respectively. The biological functions and related signaling pathways of DEMs were analyzed using the David and KOBAS databases. Subsequently, a protein-protein interaction (PPI) network was established to screen out on which hub genes enrichment analyses should be performed, and a ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD. Results. A total of 312 DEMs, 43 DELs, and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in “chromatin silencing at rDNA,” “telomere organization,” and “negative regulation of gene expression, epigenetic.” PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which ubiquitin C (UBC) was the most important. Hub genes were mainly enriched in “cellular protein metabolic process” functions. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 73 predicted miRNAs, 10 DELs, and 15 DECs. The LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network. Conclusions. Our findings provide a novel perspective on the potential role of exosomal-associated ceRNA network regulation of the pathogenesis of CHD.
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spelling doaj-art-f912578fb03f49bbb2482ffc3d013d542025-02-03T05:44:47ZengWileyCardiology Research and Practice2090-80162090-05972021-01-01202110.1155/2021/66821836682183Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart DiseaseJia Mao0Yufei Zhou1Licheng Lu2Ping Zhang3Runhua Ren4Yaqiong Wang5Jing Wang6Emergency Department, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi 214000, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, ChinaDepartment of Cardiology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan 215300, Jiangsu, ChinaEmergency Department, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi 214000, Jiangsu, ChinaDepartment of Geriatric Medicine, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, Jiangsu, ChinaDepartment of Geriatric Medicine, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, Jiangsu, ChinaDepartment of Geriatric Medicine, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, Jiangsu, ChinaBackground. Accumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associated ceRNA networks in CHD. Methods. Data from 6 CHD patients and 32 normal controls were downloaded from the ExoRBase database. CHD and normal controls were compared by screening differentially expressed mRNAs (DEMs), lncRNAs (DELs), and circRNAs (DECs) in serum exosomes. MicroRNAs (miRNAs) targeting DEMs were predicted using the Targetscan and miRanda databases, and miRNAs targeted by DELs and DECs were predicted using the miRcode and starBase databases, respectively. The biological functions and related signaling pathways of DEMs were analyzed using the David and KOBAS databases. Subsequently, a protein-protein interaction (PPI) network was established to screen out on which hub genes enrichment analyses should be performed, and a ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD. Results. A total of 312 DEMs, 43 DELs, and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in “chromatin silencing at rDNA,” “telomere organization,” and “negative regulation of gene expression, epigenetic.” PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which ubiquitin C (UBC) was the most important. Hub genes were mainly enriched in “cellular protein metabolic process” functions. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 73 predicted miRNAs, 10 DELs, and 15 DECs. The LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network. Conclusions. Our findings provide a novel perspective on the potential role of exosomal-associated ceRNA network regulation of the pathogenesis of CHD.http://dx.doi.org/10.1155/2021/6682183
spellingShingle Jia Mao
Yufei Zhou
Licheng Lu
Ping Zhang
Runhua Ren
Yaqiong Wang
Jing Wang
Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
Cardiology Research and Practice
title Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
title_full Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
title_fullStr Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
title_full_unstemmed Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
title_short Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
title_sort identifying a serum exosomal associated lncrna circrna mirna mrna network in coronary heart disease
url http://dx.doi.org/10.1155/2021/6682183
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