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Long noncoding RNAs (lncRNAs) play critical and complex roles in regulating various biological processes of periodontitis. This bioinformatic study aims to construct a putative competing endogenous RNA (ceRNA) network by integrating lncRNA, miRNA and mRNA expression, based on high-throughput RNA sequencing and microarray data about periodontitis.
University of Leipzig researchers constructed a lncRNA-associated ceRNA network from miRNA and mRNA expression profiles . Gene Ontology enrichment analysis and pathway analysis were performed using the Gene Ontology website and Kyoto Encyclopedia of Genes and Genomes. A protein-protein interaction network was constructed based on the Search Tool for the retrieval of Interacting Genes/Proteins. Transcription factors (TFs) of differentially expressed genes were identified based on TRANSFAC database and then a regulatory network was constructed.
Through constructing the dysregulated ceRNA network, 6 genes (HSPA4L, PANK3, YOD1, CTNNBIP1, EVI2B, ITGAL) and 3 miRNAs (miR-125a-3p, miR-200a, miR-142-3p) were detected. Three lncRNAs (MALAT1, TUG1, FGD5-AS1) were found to target both miR-125a-3p and miR-142-3p in this ceRNA network. Protein-protein interaction network analysis identified several hub genes, including VCAM1, ITGA4, UBC, LYN and SSX2IP. Three pathways (cytokine-cytokine receptor, cell adhesion molecules, chemokine signaling pathway) were identified to be overlapping results with the previous bioinformatics studies in periodontitis. Moreover, 2 TFs including FOS and EGR were identified to be involved in the regulatory network of the differentially expressed genes-TFs in periodontitis.
These findings suggest that 6 mRNAs (HSPA4L, PANK3, YOD1, CTNNBIP1, EVI2B, ITGAL), 3 miRNAs (hsa-miR-125a-3p, hsa-miR-200a, hsa-miR-142-3p) and 3 lncRNAs (MALAT1, TUG1, FGD5-AS1) might be involved in the lncRNA-associated ceRNA network of periodontitis. This study sought to illuminate further the genetic and epigenetic mechanisms of periodontitis through constructing an lncRNA-associated ceRNA network.
Dysregulated ceRNA network of (A) green and (B) turquoise module
In the ceRNA network, it was shown that 3 lncRNAs (TUG1, FGD5-AS1, MALAT1) directly targeted both miR-125a-3p and miR-142-3p. There was no lncRNA, which directly targeted both miR-125a-3p and miR-200a. Eighteen lncRNAs directly targeted both miR-142-3p and miR-200a, including RP4, RP5, RP11, GS1, PART1, AC, KB, BX, MEG3, NXF4, TTTY2, TTTY2B, ZNRD1-AS1, WDFY3-AS2, MCM3AP-AS1, ENTPD3-AS1, WDFY3-AS2 and LY86-AS1. Based on these results in the ceRNA network, it was believed that compared with the other lncRNAs, these 3 lncRNAs (TUG1, FGD5-AS1, MALAT1) played more significant functions in the whole ceRNA network.
