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Published on: September 15, 2018
Reconstruction and analysis of potential biomarkers for hypertrophic cardiomyopathy based on a competing endogenous
Jin-Yan Chen1,2, Zhang-Xin Xie3, Jia-Zhen Dai4
1Institute for Immunology, Fujian Academy of Medical Sciences, No. 7 Wusi Road, Fuzhou, 350001, China. chenjy1974@163.com.
Insights
This study reveals a novel long noncoding RNA (lncRNA)-associated competing RNA (ceRNA) network in hypertrophic cardiomyopathy (HCM). The lncRNA LINC00310 was found to be decreased in HCM patients, suggesting its role in disease pathogenesis.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Research
- Epigenetics
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart condition.
- The precise molecular mechanisms driving HCM pathogenesis, particularly involving long noncoding RNA (lncRNA)-associated competing RNA (ceRNA) networks, remain largely unelucidated.
Purpose of the Study:
- To investigate the role of lncRNA-associated ceRNA networks in the pathogenesis of hypertrophic cardiomyopathy (HCM).
- To identify key lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) involved in HCM development.
Main Methods:
- Microarray analysis of 520 lncRNAs and 371 mRNAs, and sequencing of 33 miRNAs from plasma of HCM patients and healthy controls.
- Prediction and integration of lncRNA-miRNA and miRNA-mRNA interactions to construct a ceRNA network.
- Quantitative real-time polymerase chain reaction (qRT-PCR) validation and Gene Ontology (GO) and pathway analyses.
Main Results:
- A ceRNA network comprising eight lncRNAs, three miRNAs, and 22 mRNAs was constructed.
- lncRNA RP11-66N24.4 and LINC00310 were identified as significant nodes within the network.
- LINC00310 expression was significantly downregulated in HCM patients and associated with cardiovascular development and the cGMP-PKG signaling pathway.
Conclusions:
- A novel lncRNA-related ceRNA network implicated in hypertrophic cardiomyopathy (HCM) has been identified.
- The lncRNA LINC00310 may play a crucial role in HCM pathogenesis, offering potential therapeutic targets.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA-miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA-mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.
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