Dataset Information

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA-miRNA-mRNA Regulatory Network.

ABSTRACT: Purpose:This research explores the aberrant expression of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in pterygium. A competitive endogenous RNA (ceRNA) network was constructed to elucidate the molecular mechanisms in pterygium. Methods:We obtained the differentially expressed mRNAs based on three datasets (GSE2513, GSE51995, and GSE83627), and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed lncRNAs (DELs) data by published literature. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and gene set enrichment analysis (GSEA) analysis were performed. DEmiRs were verified in GSE21346, and the regulatory network of hub mRNAs, DELs, and DEmiRs were constructed. Results:Overall, 40 upregulated and 40 downregulated differentially expressed genes (DEGs) were obtained. The KEGG enrichment showed the DEGs mainly involved in extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. The GSEA results showed that cornification, keratinization, and cornified envelope were significantly enriched. The validation outcome confirmed six upregulated DEmiRs (miR-766-3p, miR-184, miR-143-3p, miR-138-5p, miR-518b, and miR-1236-3p) and two downregulated DEmiRs (miR-200b-3p and miR-200a-3p). Then, a ceRNA regulatory network was constructed with 22 upregulated and 15 downregulated DEmiRs, 4 downregulated DELs, and 26 upregulated and 33 downregulated DEGs. The network showed that lncRNA SNHG1/miR-766-3p/FOS and some miRNA-mRNA axes were dysregulated in pterygium. Conclusions:Our study provides a novel perspective on the regulatory mechanism of pterygium, and lncRNA SNHG1/miR-766-3p/FOS may contribute to pterygium development.

SUBMITTER: Xu N

PROVIDER: S-EPMC7425729 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA-miRNA-mRNA Regulatory Network.

Xu Nuo N Cui Yi Y Dong Jiaxing J Huang Li L

Investigative ophthalmology & visual science 20200701 8

<h4>Purpose</h4>This research explores the aberrant expression of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in pterygium. A competitive endogenous RNA (ceRNA) network was constructed to elucidate the molecular mechanisms in pterygium.<h4>Methods</h4>We obtained the differentially expressed mRNAs based on three datasets (GSE2513, GSE51995, and GSE83627), and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed lncRNAs (DELs) data ...[more]

PMID: 32645133

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Project description:BackgroundCalcified aortic valve disease (CAVD) is one of the most common valvular heart diseases in the elderly population. However, no effective medical treatments have been found to interfere with the progression of CAVD, and specific molecular mechanisms of CAVD remain unclear.Materials and methodsTranscriptome sequencing data of GSE55492 and GSE148219 were downloaded from the European Nucleotide Archive, and the microarray dataset, GSE12644 was acquired from the Gene Expression Omnibus database. Software, including FastQC, HISAT2, samtools, and featureCounts was applied to generate the read count matrix. The "Limma" package in R was utilized to analyze differentially expressed genes (DEGs). Thereafter, weighted gene co-expression network analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the protein-protein interaction (PPI) network were used to identify hub genes associated with CAVD, which were further validated by receiver operating characteristic curve (ROC) analysis using GSE12644. The long non-coding RNA (LncRNA)-mediated regulatory network was established based on the differentially expressed LncRNAs and hub genes, which were detected using quantitative real-time PCR (qRT-PCR) in clinical samples and valve interstitial cells. Moreover, CIBERSORT was used to calculate the expression distribution of immune cell infiltration in CAVD.ResultsA total of 126 DEGs were included in the PPI network. PI3K-Akt signaling pathway, ECM-receptor interaction, hematopoietic cell lineage, cell adhesion molecules, and focal adhesion were the most enriched pathways revealed by KEGG. Four LncRNAs, including TRHDE-AS1, LINC00092, LINC01094, and LINC00702 were considered the differentially expressed LncRNA. SPP1, TREM1, GPM6A, CCL19, CR1, NCAM1, CNTN1, TLR8, SDC1, and COL6A6 were the 10 hub genes identified to be associated with CAVD. Moreover, the calcified aortic valve samples had a greater level of Tregs, naïve B cells, and M0 macrophages than the noncalcified ones, whereas CAVD samples had a lower M2 macrophage expression compared to the noncalcified valve tissues.ConclusionThe current study identified SPP1, TREM1, TLR8, SDC1, GPM6A, and CNTN1 as hub genes that could potentially be associated with CAVD. The LINC00702-miR-181b-5p-SPP1 axis might participate in the development of CAVD. Additionally, M2 macrophages, Tregs, naïve B cells, and M0 macrophages might possibly play a role in the initiation of CAVD.

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Dataset Information

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA-miRNA-mRNA Regulatory Network.

Publications

Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA-miRNA-mRNA Regulatory Network.

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