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Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non?coding RNAs in hepatic fibrosis.

ABSTRACT: Hepatic fibrosis (HF), one of the leading global health problems, is defined as aberrant and excess production of extracellular matrix components. The pathogenesis of HF is complex and poorly understood. Long non?coding RNAs (LncRNAs) can interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate the expression of target genes, which play a significant role in the initiation and progression of HF. In the present study, the LncRNA?associated ceRNA network was reconstructed based on LncRNA, miRNA and mRNA expression profiles that were downloaded from National Center for Biotechnology Information Gene Expression Omnibus. Bioinformatics assessments including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed with Database for Annotation, Visualization and Integration Discovery. The ceRNA network was composed of 220 LncRNA nodes, 24 miRNA nodes, 164 mRNA nodes and 1,149 edges. Functional assays identified that a total of 338 GO terms and 25 pathways, including regulation of cytokine and collagen, and the transforming growth factor?? and Toll?like receptor signaling pathways, were significantly enriched. In addition, 4 LncRNAs (NONMMUT036242, XR_877072, XR_378619 and XR_378418) were highly related to HF and thereby chosen as key LncRNAs. The present study uncovered a ceRNA network that could further the understanding of the mechanisms underlying HF development and provide potential novel markers for clinical diagnosis and targets for treatment.

SUBMITTER: Jiang H

PROVIDER: S-EPMC6797987 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non‑coding RNAs in hepatic fibrosis.

Jiang Hui H Wu Furong F Jiang Nannan N Gao Jiarong J Zhang Jiafu J

Molecular medicine reports 20190913 5

Hepatic fibrosis (HF), one of the leading global health problems, is defined as aberrant and excess production of extracellular matrix components. The pathogenesis of HF is complex and poorly understood. Long non‑coding RNAs (LncRNAs) can interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate the expression of target genes, which play a significant role in the initiation and progression of HF. In the present study, the LncRNA‑associated ceRNA network was reconstructed ...[more]

PMID: 31545470

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Project description:BackgroundIncreasing evidence has suggested that non-coding RNAs (ncRNAs) play critical roles in the pathogenesis of diabetic retinopathy (DR), but their underlying mechanisms remain unclear. The purpose of this study was to determine latent key genes and to structure a competing endogenous RNA (ceRNA) regulatory network to discover the potential molecular mechanisms governing the effects of high glucose on human retinal endothelial cells (HRECs).MethodsWe obtained microarray data for long non-coding RNA (lncRNA) and mRNA of high-glucose-induced HREC samples from NCBI GEO datasets. The ceRNA network was screened using intersecting prediction results from miRcode, TargetScan, miRTarBase and miRDB. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and hub genes were obtained using the cytoHubba app. The ClusterProfiler package was applied for performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of key RNAs was verified using the qRT-PCR method. A key ceRNA subnetwork was constructed based on the criticality of the genes and its binding sites were verified by luciferase reporter assay. The viability and apoptosis of HRECs were tested using the transfection of the miR-449c inhibitor.ResultsA total of 3,328 lncRNAs and 2,017 mRNAs were screened for differentially expressed (DE) profiles. The newly constructed ceRNA network was composed of 410 lncRNAs, 35 miRNAs and 122 mRNAs. The 10 hub genes were identified through the PPI network. GO and KEGG analysis revealed that DE mRNAs were mainly related to the positive regulation of the mRNA catabolic process, cell polarity, and the G1/S transition of mitotic and cell cycle signaling pathways. QRT-PCR was used to verify RNAs and the most important genes were screened out. A key ceRNA subnetwork OIP5-AS1/miR-449c/MYC was established. The binding site was verified by luciferase reporter assay. The expression levels of OIP5-AS1 and MYC increased after miR-449c inhibitor transfection, miR-449c decreased, HRECs activity increased, and apoptosis decreased, compared with the control group.ConclusionWe successfully built the key ceRNA subnetwork, OIP5-AS1/miR-449c/MYC, by applying the GEO database for data analysis and mining. The results from the ceRNA network allow us to better understand the effect of ncRNAs on HRECs under hyperglycemic conditions and the pathogenesis of DR.

Dataset Information

Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non?coding RNAs in hepatic fibrosis.

Publications

Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non‑coding RNAs in hepatic fibrosis.

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