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Identifying a Serum Exosomal-Associated lncRNA/circRNA-miRNA-mRNA Network in Coronary Heart Disease
Jia Mao1, Yufei Zhou2, Licheng Lu3
1Emergency Department, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi 214000, Jiangsu, China.
Insights
This study explores exosomal competing endogenous RNA (ceRNA) networks in coronary heart disease (CHD). Key ceRNA axes involving lncRNAs, circRNAs, miRNAs, and mRNAs were identified, offering new insights into CHD pathogenesis.
Area of Science:
- Genomics
- Molecular Biology
- Biochemistry
Background:
- Noncoding RNAs and exosomes are increasingly recognized for their roles in coronary heart disease (CHD).
- Mechanisms of exosomal competing endogenous RNA (ceRNA) regulation in CHD remain largely uncharacterized.
- This study investigates exosomal ceRNA networks to uncover novel regulatory pathways in CHD.
Purpose of the Study:
- To identify differentially expressed molecules (mRNAs, lncRNAs, circRNAs) in serum exosomes of CHD patients.
- To construct and analyze exosomal ceRNA networks and identify key regulatory axes in CHD.
- To explore the functional implications of these networks in the pathogenesis of CHD.
Main Methods:
- Serum exosome data from CHD patients and controls were analyzed for differentially expressed mRNAs, lncRNAs, and circRNAs.
- Computational tools were used to predict miRNA targets and construct lncRNA/circRNA-miRNA-mRNA ceRNA networks.
- Functional enrichment and protein-protein interaction network analyses were performed on differentially expressed mRNAs.
Main Results:
- Significant differences in exosomal mRNAs, lncRNAs, and circRNAs were found between CHD patients and controls.
- Functional enrichment analysis highlighted roles in 'chromatin silencing at rDNA' and 'telomere organization'.
- A comprehensive exosomal ceRNA network was constructed, revealing key axes such as RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC.
Conclusions:
- The study elucidates the potential role of exosomal ceRNA networks in the pathogenesis of coronary heart disease.
- Identified ceRNA axes provide novel molecular targets for understanding and potentially treating CHD.
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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