Integrated analysis of long noncoding RNA-associated competing endogenous RNA network in periodontitis.

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. Data from 1 miRNA and 3 mRNA expression profiles were obtained to construct the lncRNA-associated ceRNA network. 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.

Li S ，Liu X ，Li H ，Pan H ，Acharya A ，Deng Y ，Yu Y ，Haak R ，Schmidt J ，Schmalz G ，Ziebolz D ... -  《-》

Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue.

Zhou RS ，Zhang EX ，Sun QF ，Ye ZJ ，Liu JW ，Zhou DH ，Tang Y ... -  《BMC CANCER》

Complex integrated analysis of lncRNAs-miRNAs-mRNAs in oral squamous cell carcinoma.

This study aims to reveal regulatory network of lncRNAs-miRNAs-mRNAs in oral squamous cell carcinoma (OSCC) through gene expression data. Differentially expressed lncRNAs, miRNAs and mRNAs (cut-off: False discovery rate (FDR)<0.05 and |fold change|>1.5) were unveiled by package edgeR of R. Cox regression analysis was performed to screen prognostic factors in OSCC related with overall survival (OS) and relapse-free survival (RFS). Protein-protein interaction (PPI) network was constructed for differentially expressed mRNAs using BioGRID, HPRD and DIP. Key hub genes were identified from top 100 differentially expressed mRNAs ranked by betweenness centrality using recursive feature elimination. LncRNA-miRNA and miRNA-mRNA regulatory network were constructed and combined into ceRNAs regulatory network. Gene ontology biological terms and Kyoto Encyclopedia of Genes and Genomes pathways were identified using Fisher's exact test. A total of 929 differentially expressed mRNAs, 23 differentially expressed lncRNAs and 29 differentially expressed miRNAs were identified. 59 mRNAs, 6 miRNAs (hsa-mir-133a-1, hsa-mir-1-2, hsa-mir-486, hsa-mir-135b, hsa-mir-196b, hsa-mir-193b) and 6 lncRNAs (C10orf91, C2orf48, SFTA1P, FLJ41941,PART1,TTTY14) were related with OS; and 52 mRNAs, 4 miRNAs (hsa-mir-133a-1, hsa-mir-135b, hsa-mir-196b, hsa-mir-193b) and 2 lncRNAs (PART1, TTTY14) were associated with RFS. A support vector machine (SVM) classifier containing 37 key hub genes was obtained. A ceRNA regulatory network containing 417 nodes and 696 edges was constructed. ECM-receptor interaction, cytokine-cytokine receptor interaction, focal adhesion, arachidonic acid metabolism, and p53 signaling pathway were significantly enriched in the network. These findings uncover the pathogenesis of OSCC and might provide potential therapeutic targets.

Li S ，Chen X ，Liu X ，Yu Y ，Pan H ，Haak R ，Schmidt J ，Ziebolz D ，Schmalz G ... -  《-》

Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma.

Wang LX ，Wan C ，Dong ZB ，Wang BH ，Liu HY ，Li Y ... -  《MEDICAL SCIENCE MONITOR》

Identification of Functional Genes in Pterygium Based on Bioinformatics Analysis.

The competing endogenous RNA (ceRNA) network regulatory has been investigated in the occurrence and development of many diseases. This research aimed at identifying the key RNAs of ceRNA network in pterygium and exploring the underlying molecular mechanism. Differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were obtained from the Gene Expression Omnibus (GEO) database and analyzed with the R programming language. LncRNA and miRNA expressions were extracted and pooled by the GEO database and compared with those in published literature. The lncRNA-miRNA-mRNA network was constructed of selected lncRNAs, miRNAs, and mRNAs. Metascape was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on mRNAs of the ceRNA network and to perform Protein-Protein Interaction (PPI) Network analysis on the String website to find candidate hub genes. The Comparative Toxicogenomic Database (CTD) was used to find hub genes closely related to pterygium. The differential expressions of hub genes were verified using the reverse transcription-real-time fluorescent quantitative PCR (RT-qPCR). There were 8 lncRNAs, 12 miRNAs, and 94 mRNAs filtered to construct the primary ceRNA network. A key lncRNA LIN00472 ranking the top 1 node degree was selected to reconstruct the LIN00472 network. The GO and KEGG pathway enrichment showed the mRNAs in ceRNA networks mainly involved in homophilic cell adhesion via plasma membrane adhesion molecules, developmental growth, regulation of neuron projection development, cell maturation, synapse assembly, central nervous system neuron differentiation, and PID FOXM1 PATHWAY. According to the Protein-Protein Interaction Network (PPI) analysis on mRNAs in LINC00472 network, 10 candidate hub genes were identified according to node degree ranking. Using the CTD database, we identified 8 hub genes closely related to pterygium; RT-qPCR verified 6 of them were highly expressed in pterygium. Our research found LINC00472 might regulate 8 hub miRNAs (miR-29b-3p, miR-183-5p, miR-138-5p, miR-211-5p, miR-221-3p, miR-218-5p, miR-642a-5p, miR-5000-3p) and 6 hub genes (CDH2, MYC, CCNB1, RELN, ERBB4, RB1) in the ceRNA network through mainly PID FOXM1 PATHWAY and play an important role in the development of pterygium.

Xu Y ，Qiao C ，He S ，Lu C ，Dong S ，Wu X ，Yan M ，Zheng F ... -  《-》