Dataset Information

Reconstruction and Analysis of a Long Noncoding RNA-Associated Competing Endogenous RNA Network in Hypertrophic Cardiomypathy [array]

ABSTRACT: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopath that caused by mutations in genes encoding proteins of the cardiac sarcomere. Although multiple efforts have been made to understand the pathogenesis of HCM, the mechanisms of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM still unkown. Herein, we acquired the different expression profiles of lncRNAs (DElncRNAs) and messenger RNAs (mRNA, DEGs) by using microarray, microRNAs (DEmiRNAs) by sequencing in plasma of HCM patients and healthy controls. 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 these pairs, the ceRNA network was constructed and hub nodes were then analyzed to reconstruct subnetwork. Gene Ontology and KEGG pathways were used to analyse the mRNAs in the ceRNA. Total 520 DElncRNAs, 33 DEmiRNAs, and 371 DEGs were identified. By coexpression analysis, 682 lncRNA-mRNA pairs were identiﬁed with a coefﬁcient ≥ 0.9 and p < 0.05. The ceRNA network with 8 lncRNAs, 3 miRNAs and 22 mRNAs was constructed visualized by Cytoscape. LncRNA RP11-66N24.4 and LINC00310 are among the top 10% nodes and the associated ceRNA subnetwork may be the center of the whole ceRNA network. Furthermore, the qRT-PCR results showed that LINC00310 was signifcantly decreased in HCM patients. For LINC00310, GO analysis revealed that the biological processes was enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development and so on, and Pathway analysis was mainly enriched in cGMP-PKG signaling pathway. Our study reveals the novel lncRNA-related ceRNA network in HCM and the identified lncRNA LINC00310 may be roles in the pathogenesis mechanisms of HCM, which could provide further insight into the pathogenesis of HCM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197218 | GEO | 2022/09/28

REPOSITORIES: GEO

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Project description:Adiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts an anti-inflammation property. AdipoAI is an orally active adiponectin receptor agonist identified by our group, which can emulate APN's anti-inflammatory properties through mechanisms not fully understood. To explore AdipoAI function, we used lncRNA microarray and got differential lncRNA/mRNA expression medicated by AdipoAI. Identified as one kind of non-coding RNA with more than 200bp length, lncRNA has been demonstrated to have abundance biological functions, including anti-inflammatory response. In the current study, we performed an lncRNA microarray in LPS-induced Raw264.7 cells which pre-stimulated with AdipoAI, and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted to total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA and PPI analysis. Among all these processes, endocytosis was significantly enriched. A co-expression analysis was built based on DElncRNAs and DEmRNAs. Then, using Targetscan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation related marker genes were obtained from previous study and used for the construction of m6A related-lncRNA network using the co-expression analysis. We identified FTO as the hub gene of the network, and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO- related lncRNAs networks were validated with qRT-PCR. Finally, Macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophage and correlate with the above lncRNAs. Our work reveals that lncRNA might involve in the anti-inflammation process of AdipoAI in LPS-induced macrophages through ceRNA network and epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophage, and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.

Dataset Information

Reconstruction and Analysis of a Long Noncoding RNA-Associated Competing Endogenous RNA Network in Hypertrophic Cardiomypathy [array]

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