Department of Stomatology, Northeast Petroleum University Affiliated Hospital, Fazhan Road, High Tech District, 163000 Daqing City, Heilongjiang Province, China.
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.
Dis Markers. 2021 Mar 8;2021:8831948. doi: 10.1155/2021/8831948. eCollection 2021.
To identify the critical genetic and epigenetic biomarkers by constructing the long noncoding RNA- (lncRNA-) related competing endogenous RNA (ceRNA) network involved in irreversible pulp neural inflammation (pulpitis).
The public datasets regarding irreversible pulpitis were downloaded from the gene expression omnibus (GEO) database. The differential expression analysis was performed to identify the differentially expressed genes (DEGs) and DElncRNAs. Functional enrichment analysis was performed to explore the biological processes and signaling pathways enriched by DEGs. By performing a weighted gene coexpression network analysis (WGCNA), the significant gene modules in each dataset were identified. Most importantly, DElncRNA-DEmRNA regulatory network and DElncRNA-associated ceRNA network were constructed. A transcription factor- (TF-) DEmRNA network was built to identify the critical TFs involved in pulpitis.
Two datasets (GSE92681 and GSE77459) were selected for analysis. DEGs involved in pulpitis were significantly enriched in seven signaling pathways (i.e., NOD-like receptor (NLR), Toll-like receptor (TLR), NF-kappa B, tumor necrosis factor (TNF), cell adhesion molecules (CAMs), chemokine, and cytokine-cytokine receptor interaction pathways). The ceRNA regulatory relationships were established consisting of three genes (i.e., LCP1, EZH2, and NR4A1), five miRNAs (i.e., miR-340-5p, miR-4731-5p, miR-27a-3p, miR-34a-5p, and miR-766-5p), and three lncRNAs (i.e., XIST, MIR155HG, and LINC00630). Six transcription factors (i.e., GATA2, ETS1, FOXP3, STAT1, FOS, and JUN) were identified to play pivotal roles in pulpitis.
This paper demonstrates the genetic and epigenetic mechanisms of irreversible pulpitis by revealing the ceRNA network. The biomarkers identified could provide research direction for the application of genetically modified stem cells in endodontic regeneration.
通过构建涉及不可逆性牙髓神经炎症（牙髓炎）的长非编码 RNA（lncRNA）相关竞争性内源性 RNA（ceRNA）网络，鉴定关键的遗传和表观遗传生物标志物。
从基因表达综合（GEO）数据库中下载了关于不可逆性牙髓炎的公共数据集。进行差异表达分析以鉴定差异表达基因（DEGs）和 DE lncRNAs。进行功能富集分析以探索 DEGs 富集的生物学过程和信号通路。通过进行加权基因共表达网络分析（WGCNA），鉴定每个数据集的显著基因模块。最重要的是，构建了 DE lncRNA-DEmRNA 调控网络和 DE lncRNA 相关 ceRNA 网络。构建转录因子（TF）-DEmRNA 网络以鉴定参与牙髓炎的关键 TF。
选择了两个数据集（GSE92681 和 GSE77459）进行分析。与牙髓炎相关的 DEGs 显著富集于七个信号通路（即 NOD 样受体（NLR）、Toll 样受体（TLR）、NF-kappa B、肿瘤坏死因子（TNF）、细胞黏附分子（CAMs）、趋化因子和细胞因子-细胞因子受体相互作用途径）。建立了包含三个基因（LCP1、EZH2 和 NR4A1）、五个 miRNAs（miR-340-5p、miR-4731-5p、miR-27a-3p、miR-34a-5p 和 miR-766-5p）和三个 lncRNAs（XIST、MIR155HG 和 LINC00630）的 ceRNA 调控关系。鉴定出六个转录因子（GATA2、ETS1、FOXP3、STAT1、FOS 和 JUN）在牙髓炎中发挥关键作用。
本文通过揭示 ceRNA 网络，展示了不可逆性牙髓炎的遗传和表观遗传机制。鉴定出的生物标志物可为基因修饰干细胞在牙髓再生中的应用研究提供方向。
