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. 2019 Nov;18(5):4011-4021.
doi: 10.3892/etm.2019.8035. Epub 2019 Sep 23.

Construction of a lncRNA-miRNA-mRNA network to determine the regulatory roles of lncRNAs in psoriasis

Affiliations

Construction of a lncRNA-miRNA-mRNA network to determine the regulatory roles of lncRNAs in psoriasis

Qianqian Zhou et al. Exp Ther Med. 2019 Nov.

Abstract

Psoriasis is a chronic inflammatory skin disorder that impairs the quality of life of affected patients. Emerging studies indicate that certain long non-coding RNAs (lncRNAs) have important roles in psoriasis. However, the exact functions of lncRNAs and their regulatory mechanisms as competitive endogenous RNAs (ceRNAs) in psoriasis have remained to be fully elucidated. In the present study, differentially expressed lncRNAs, microRNAs (miRNAs) and mRNAs were identified by analyzing public datasets, and a psoriasis-associated lncRNA-miRNA-mRNA network was constructed based on the ceRNA theory. Furthermore, previously validated abnormally expressed miRNAs in psoriasis were identified by a systematic literature search in the PubMed and Web of Science databases, and a specific miRNA-associated lncRNA-miRNA-mRNA sub-network was extracted. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID 6.8. A total of 253 lncRNAs, 106 miRNAs and 1,156 mRNAs were identified as being differentially expressed between psoriasis skin and healthy control skin. The present study identified two key lncRNAs that may potentially have a role in the pathogenesis of psoriasis: AL035425.3 and Prader Willi/Angelman region RNA 6. This integrative analysis enhances the understanding of the molecular mechanism of psoriasis and may provide novel therapeutic targets for the treatment of psoriasis.

Keywords: competing endogenous RNAs; long non-coding RNAs; network; psoriasis.

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Figures

Figure 1.
Figure 1.
Identification of differentially expressed lncRNAs, mRNAs and miRNAs in psoriasis. (A) Integrated analysis of upregulated (top left) and downregulated (top right) lncRNAs. (B) Integrated analysis of upregulated (bottom left) and downregulated (bottom right) mRNAs. (B) Heat map displaying differential miRNA expression in psoriasis within the GSE31037 dataset. lncRNA, long non-coding RNA; miR/miRNA, microRNA; hsa, Homo sapiens.
Figure 2.
Figure 2.
Biological function and pathway analysis of differentially expressed genes (top 15). (A) GO biological process enrichment analysis of upregulated mRNAs. (B) GO biological process enrichment analysis of downregulated mRNAs. (C) KEGG pathway analysis of upregulated mRNAs. (D) KEGG pathway analysis of downregulated mRNAs. KEGG, Kyoto Encyclopedia of Genes and Genomes; GO, gene ontology.
Figure 3.
Figure 3.
Construction of upregulated lncRNA-mediated ceRNA network. Green nodes, lncRNAs; red nodes, miRNAs; blue nodes, mRNAs. lncRNA, long non-coding RNA; miR/miRNA, microRNA; hsa, Homo sapiens.
Figure 4.
Figure 4.
Construction of downregulated lncRNA-mediated ceRNA network. Green nodes, lncRNAs; red nodes, miRNAs; blue nodes, mRNAs. lncRNA, long non-coding RNA; miR/miRNA, microRNA; hsa, Homo sapiens.
Figure 5.
Figure 5.
Identification of key lncRNA analysis. (A) The degree distribution of lncRNAs in the downregulated lncRNA-mediated ceRNA network are presented. (B) Expression level of two key lncRNAs in psoriasis skin and healthy control skin. (C) Key downregulated lncRNA-mediated biological processes analysis. lncRNA, long non-coding RNA; ceRNA, competing endogenous RNA; PWAR6, Prader Willi/Angelman region RNA 6.
Figure 6.
Figure 6.
Construction of a specific literature confirmed miRNA-associated lncRNA-miRNA-mRNA sub-network. (A) Intersection of confirmed upregulated miRNAs and miRNAs from downregulated lncRNA-mediated ceRNA network. (B) Confirmed differentially expressed miRNA-associated lncRNA-miRNA-mRNA sub-network. Green nodes, lncRNAs; red nodes, miRNAs; blue nodes, mRNAs. lncRNA, long non-coding RNA; miR/miRNA, microRNA; hsa, Homo sapiens.

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