Dataset Information

Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

ABSTRACT: Salt-sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non-coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH-associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulatory network included 23 ceRNA loops, and six hub RNAs (lnc-ILK-8:1, lnc-OTX1-7:1, lnc-RCAN1-6:1, GIMAP8, SUV420H1 and PIGV) were identified for further population validation. The ceRNA correlations among lnc-OTX1-7:1, hsa-miR-361-5p and GIMAP8 were confirmed in SSH and SRH patients. A larger-sample validation confirmed that GIMAP8, SUV420H1 and PIGV were differentially expressed between the SSH and SRH groups. In addition, SUV420H1 was included in the SSH screening model, and the area under the curve of the model was 0.720 (95% CI: 0.624-0.816). Our study explored the transcriptome profiles of SSH and constructed a ceRNA network to help elucidate the mechanism of SSH. In addition, SUV420H1 was identified as a hub element that participates in SSH transcriptional regulation and as a potential biomarker for the early diagnosis of SSH.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7379024 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

Zhang Ling L Qi Han H Liu Zheng Z Peng Wen-Juan WJ Cao Han H Guo Chun-Yue CY Sun Yan-Yan YY Pao Christine C Xiang Yu-Tao YT

Journal of cellular and molecular medicine 20200515 13

Salt-sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non-coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH-associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulato ...[more]

PMID: 32410228

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Project description:BackgroundThis study aimed to identify the biomarkers related to myocardial infarction based on building lncRNA-miRNA-mRNA ceRNA regulation network.MethodsThe expression profile data were obtained from the Gene Expression Omnibus database. The differentially expressed RNAs (DElncRNAs, DEmiRNAs, and DEmRNAs) were analyzed using the limma package of R. In addition, the differential myocardial infarction-related genes were obtained and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway on the differential myocardial infarction-related genes were analyzed. The co-expression network of lncRNA-mRNA was constructed, and the Kyoto Encyclopedia of Genes and Genomes pathway of such a co-expression network was analyzed. Moreover, the lncRNA-miRNA-mRNA ceRNA network associated with myocardial infarction was built, and the key biomarkers of the ceRNA network were verified using the GSE141512 and GSE66752 datasets.ResultsIn total, we acquired 51 DElncRNAs, 276 DEmiRNAs, and 1200 DEmRNAs as well as 291 differential myocardial infarction-related genes. Moreover, the co-expression network of lncRNA-mRNA was built, and mRNAs were found to be associated with 109 Kyoto Encyclopedia of Genes and Genomes pathways (the target gene of RP3-394A18.1 was significantly related to lipid and atherosclerosis). In addition, the ceRNA network related to myocardial infarction was constructed, and the dataset analyses of the RNAs were validated between the myocardial infarction and normal groups. It was also found that the expression levels of hsa-miR-1291 and Retinoid acid receptor-related orphan receptor α (RORA) in the myocardial infarction group were noticeably lower than those in the normal group, whereas the expression levels of ENTPD1, QSOX1, and TIMP2 in the myocardial infarction group were noticeably higher than those in the normal group.ConclusionIn this study, we built a ceRNA regulation network of myocardial infarction. This study could help identify the biomarkers related to myocardial infarction.

Project description:BackgroundAortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.MethodsExpression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.ResultsWe identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value <0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).ConclusionThis is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

Project description:BackgroundMilk fat is one of the main reference elements for evaluating milk quality and is a primary objective trait in dairy cattle breeding. In recent years, circular RNAs (circRNAs) have been found to play crucial roles in many biological processes. However, the function and expression profiles of circRNAs in milk fat synthesis in cows are not completely understood. We performed RNA sequencing to analyze the genome-wide expression of circRNA transcripts in bovine mammary epithelial cells (BMECs) from cows with extreme differences in milk fat percentage. We identified candidate differential circRNAs associated with milk fat metabolism using functional enrichment analysis and constructed a lipid metabolism-related competing endogenous RNA (ceRNA) interactive regulatory network.ResultsA total of 290 circRNAs were significantly differentially expressed (DE-circRNAs) in high milk fat percentage (HMF) cows compared to that in low milk fat percentage (LMF) cows. Of the 290 circRNAs, 142 were significantly upregulated and 148 were significantly downregulated. Enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) identified four DE-circRNAs (circ_0001122, circ_0007367, circ_0018269, and circ_0015179) that potentially regulate milk fat metabolism. Among them, circ_0001122, circ_0007367, and circ_0015179 had relatively high expression levels in cow mammary gland tissue compared to other tissues (heart, liver, kidney, uterus, ovaries, and small intestine) of cows. The regulatory networks circ_0001122:miR-12043:LIPG, circ_0007367:miR-331-3p:CIDEA/PML, and circ_0018269:miR-11989:RORC/HPX are potential networks to explore the mechanism of milk fat regulation.ConclusionsThese results reveal the possible role of circRNAs in milk fat metabolism in dairy cows. Several important circRNAs and ceRNAs affecting milk fat synthesis were identified, providing insights into the complex biology of milk fat synthesis as well as a novel theoretical perspective for future research on lactation, milk quality, and breed improvement in dairy cows.

Dataset Information

Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

Publications

Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

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