Dataset Information

Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

ABSTRACT: OBJECTIVES:To identify long noncoding RNAs (lncRNAs) and construct a competing endogenous RNA (ceRNA) network for essential hypertension. METHODS:An RNA microarray and two-step quantitative real-time PCR were applied to identify differentially expressed RNAs (DE-RNAs), and a luciferase assay was performed to explore the binding relationship between RNAs. A generalized linear model and logistic regression model were used to analyze the associations between different RNAs and of RNAs with hypertension. Receiver operating characteristic curve analysis was executed to evaluate the diagnostic performance. Bioinformatics analysis was applied for network construction. RESULTS:In total, 439 DE-RNAs (387 lncRNAs and 52 mRNAs) were identified in the microarray, and 71 'lncRNA-miRNA-mRNA' loops formed the ceRNA network. The first validation confirmed that five RNAs (NR_104160, lnc-GPR63-8:1, lnc-HPRT1-9:1, ID1 and RSL24D1) were significantly upregulated in hypertensives (P < 0.05). NR_104160 was significantly associated with hypertension (OR = 2.863, 95% CI: 1.143-7.172; P = 0.025) after adjusting for confounding factors. NR_104160 was included in the hypertension diagnostic model, with an area under the curve of 0.852 (95% CI: 0.761-0.944). In the second validation, NR_104160 showed a constant significant difference (P = 0.001). An elevated expression level of NR_104160 was associated with the expression of ID1 (? = 0.2235, P = 0.005). Luciferase assays showed hsa-miR-101-3p stimulation significantly inhibited the reporter gene activation ability of the NR_104160 wild-type plasmid (P < 0.001). CONCLUSIONS:Our study constructed a ceRNA network to provide hypotheses regarding the mechanism of hypertension development. lncRNA-NR_104160 was identified as a hub element that participates in hypertension transcriptional regulation and as a potential biomarker.

SUBMITTER: Peng W

PROVIDER: S-EPMC7653565 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

Peng Wenjuan W Cao Han H Liu Kuo K Guo Chunyue C Sun Yanyan Y Qi Han H Liu Zheng Z Xie Yunyi Y Liu Xiaohui X Li Bingxiao B Zhang Ling L

American journal of translational research 20201015 10

<h4>Objectives</h4>To identify long noncoding RNAs (lncRNAs) and construct a competing endogenous RNA (ceRNA) network for essential hypertension.<h4>Methods</h4>An RNA microarray and two-step quantitative real-time PCR were applied to identify differentially expressed RNAs (DE-RNAs), and a luciferase assay was performed to explore the binding relationship between RNAs. A generalized linear model and logistic regression model were used to analyze the associations between different RNAs and of RNA ...[more]

PMID: 33194014

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Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.

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Dataset Information

Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

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Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension.

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