Identification of novel key lncRNAs involved in periodontitis by weighted gene co-expression network analysis

Abstract

Background and objective: Periodontitis is a multifactorial disease that can lead to the progressive destruction of dental support tissue. However, the detailed mechanisms and specific biomarkers involved in periodontitis remain to be further studied. Recently, long non-coding RNAs (lncRNAs) have been found to play a more important role than other types of RNAs. In our study, we analysed the expression of lncRNAs in periodontitis by analysing GSE16134.

Material and methods: We identified highly correlated genes by analysing GSE16134 with weighted gene co-expression network analysis (WGCNA) and identified 50 hub lncRNAs that were dysregulated. Then, we used the Linear Models for Microarray Data (Limma) package to identify the hub lncRNAs that were differentially expressed (DElncRNAs). The ceRNA co-expression network data were obtained from several sites, including miRcode, and were used to assess the potential WGCNA function of hub DElncRNAs in periodontitis. Besides, we divided the samples into LBX2-AS1 high and low expression group by the expression level of LBX2-AS1 and calculated DEG by Limma package. Furthermore, we performed GO function, KEGG pathway and GSEA enrichment of DEGs.

Results: In the analysis, we identified 50 hub lncRNAs that may play important roles in periodontitis. Then, we used the Limma package to identify 3 hub DElncRNAs (LINC00687, LBX2-AS1 and LINC01566). We elucidated the potential function of the hub DElncRNA LBX2-AS1 in periodontitis by constructing a co-expression network of lncRNA-miRNA-mRNA interactions. Totally, 573 DEGs (354 up- and 219 downregulated) in periodontitis samples were identified. DEGs were enriched in different GO terms and pathways, such as neutrophil degranulation, neutrophil activation, neutrophil activation involved in immune response, neutrophil-mediated immunity, antigen processing and presentation, JAK-STAT signalling pathway, natural killer cell-mediated cytotoxicity, EGFR tyrosine kinase inhibitor resistance, phosphatidylinositol signalling system and Vascular Endothelial Growth Factor (VEGF) signalling pathway.

Conclusion: In our study, we found that 3 hub DElncRNAs (LINC00687, LBX2-AS1 and LINC01566) may be involved in the pathogenesis of periodontitis based on WGCNA and Limma analysis. Our study aimed to elucidate the mechanisms involved in periodontitis at the genetic and epigenetic levels by constructing a ceRNA network associated with lncRNA. Besides, identification DEGs of differential LBX2-AS1 and functional annotation showed that LBX2-AS1 might be associated with periodontitis.

Keywords: WGCNA; differentially expressed genes; gene module; hub gene; long non-coding RNA; periodontitis.