Identification of novel key lncRNAs involved in periodontitis by weighted gene co-expression network analysis
Identification of novel key lncRNAs involved in periodontitis by weighted gene co-expression network analysis
复制标题
通过加权基因共表达网络分析鉴定与牙周炎相关的新型关键lncRNA
DOI：
10.1111/jre.12693
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发表时间：
2019-09-12
影响因子：
3.5
通讯作者：
Liu, Jian-Guo
中科院分区：
文献类型：
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作者：
Jin, Su-Han;Zhou, Rui-Hao;Liu, Jian-Guo
背景与目的牙周炎是一种多因素疾病，可导致牙齿支持组织的进行性破坏。然而，涉及牙周炎的详细机制和特定的生物标志物仍有待进一步研究。最近发现，与其他类型的RNA相比，长非编码RNA(LncRNAs)发挥着更重要的作用。在我们的研究中，我们通过分析GSE16134分析了lncRNAs在牙周炎中的表达。材料与方法我们通过加权基因共表达网络分析(WGCNA)对GSE16134进行分析，找出了高度相关的基因，并鉴定了50个HUB LncRNAs。然后，我们使用微阵列数据的线性模型(LIMMA)包来识别差异表达的中枢LncRNAs(DElncRNAs)。从包括miRcode在内的几个位置获得了Cerna共表达网络数据，并用于评估HUB DElncRNAs在牙周炎中潜在的WGCNA功能。根据LBX2-AS1的表达水平将标本分为LBX2-AS1高表达组和低表达组，用LIMMA软件包计算DEG。此外，我们还对DEGS的GO功能、KEGG途径和GSEA进行了研究。结果在分析中，我们发现了50个可能在牙周炎中起重要作用的中枢LncRNAs。然后，我们使用LIMMA软件包对3个HUB DElncRNAs(LINC00687、LBX2-AS1和LINC01566)进行了鉴定。我们通过构建lncRNA-miRNA-mRNA相互作用的共表达网络，阐明了HUB DElncRNA LBX2-AS1在牙周炎中的潜在功能。总共在牙周炎样本中鉴定出573个DGs(354个上调和219个下调)。DEGS富含不同的GO术语和途径，如中性粒细胞脱颗粒、中性粒细胞激活、参与免疫反应的中性粒细胞激活、中性粒细胞介导的免疫、抗原处理和递呈、JAK-STAT信号通路、自然杀伤细胞介导的细胞毒作用、EGFR酪氨酸激酶抑制剂抵抗、磷脂酰肌醇信号系统和血管内皮生长因子(VEGF)信号通路。结论通过WGCNA和LIMMA分析，发现3个Hub DElncRNAs(LINC00687、LBX2-AS1和LINC01566)可能参与了牙周炎的发病过程。我们的研究旨在通过构建与lncRNA相关的CENA网络，从遗传和表观遗传水平阐明牙周炎的发病机制。此外，LBX2-AS1的差异鉴定和功能注释显示LBX2-AS1可能与牙周炎有关。
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.