口腔扁平苔藓lncRNA/circRNAs-miRNA-mRNA网络的综合分析

Comprehensive Analysis of lncRNA/circRNAs-miRNA-mRNA Networks of Oral Lichen Planus.

作者信息

Zhang Muyang, Miao Limin, Chen Huyan, Sun Hongying, Yang Qiaozhen

机构信息

Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Department of Geriatric Dentistry, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

出版信息

J Inflamm Res. 2025 Aug 29;18:11911-11924. doi: 10.2147/JIR.S526077. eCollection 2025.

DOI:10.2147/JIR.S526077

PMID:40908948

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12405715/

Abstract

BACKGROUND

Oral lichen planus (OLP) is T cell-mediated inflammatory disease affecting the oral mucosa, and its molecular mechanism remains poorly understood.

OBJECTIVE

This study aimed to screen for OLP-related hub genes and construct a network of competing endogenous RNAs (ceRNAs) to explore the crucial mechanisms involved in the disease.

METHODS

Proteomic and transcriptomic sequencing were performed on oral mucosa collected from OLP patients and healthy participants, respectively. Limma package was used to screen differentially expressed proteins (DEPs) and RNAs between groups. Shared genes between DEPs and DE mRNAs (DEGs) were subjected to functional enrichment analysis and protein-protein interaction (PPI) network construction. Weighted gene co-expression network analysis was used to screen for OLP-related genes. Furthermore, the OLP-related genes in the most significant PPI modules were defined as key genes, and LASSO analysis was further used to screen hub genes from the key genes. The area under curve (AUC) value was calculated from receiver operating characteristic curves to assess the diagnostic efficacy of hub genes. Finally, a ceRNAs regulatory network was constructed, and the hub genes were validated using qPCR analysis.

RESULTS

In the disease group, 103 shared DEGs (85 upregulated and 18 downregulated) were identified from both transcriptomic and proteomic data. These DEGs were involved in pathways such as antigen processing and presentation. COTL1, OAS2, HLA-A, and HLA-DPA1 were identified as hub genes. They had good diagnostic efficacy for OLP, with all AUC value exceeding 0.7 based on the transcriptomic and proteomic data. LncRNA MIR155HG regulated COTL1 and OAS2 by competitively binding to hsa-miR-1233-5p. Moreover, PCR analysis validated that these four hub genes were all highly expressed in OLP tissue compared with control tissue ( < 0.05).

CONCLUSION

mRNAs, proteins and non-coding RNAs provide clues to study the mechanisms of OLP. Furthermore, circRNAs/lncRNAs-miRNAs-mRNA networks provide more information about potential novel mechanisms and diagnostic treatments for OLP.

摘要

背景

口腔扁平苔藓（OLP）是一种由T细胞介导的影响口腔黏膜的炎症性疾病，其分子机制仍知之甚少。

目的

本研究旨在筛选与OLP相关的枢纽基因，并构建竞争性内源性RNA（ceRNA）网络，以探索该疾病的关键机制。

方法

分别对OLP患者和健康参与者的口腔黏膜进行蛋白质组学和转录组测序。使用Limma软件包筛选两组之间差异表达的蛋白质（DEP）和RNA。对DEP和差异表达mRNA（DEG）之间的共享基因进行功能富集分析和蛋白质-蛋白质相互作用（PPI）网络构建。采用加权基因共表达网络分析筛选与OLP相关的基因。此外，将最显著PPI模块中的OLP相关基因定义为关键基因，并进一步使用LASSO分析从关键基因中筛选枢纽基因。根据受试者工作特征曲线计算曲线下面积（AUC）值，以评估枢纽基因的诊断效能。最后，构建ceRNA调控网络，并使用qPCR分析验证枢纽基因。

结果

在疾病组中，从转录组和蛋白质组数据中均鉴定出103个共享的DEG（85个上调和18个下调）。这些DEG参与抗原加工和呈递等途径。COTL1、OAS2、HLA-A和HLA-DPA1被鉴定为枢纽基因。基于转录组和蛋白质组数据，它们对OLP具有良好的诊断效能，所有AUC值均超过0.7。LncRNA MIR155HG通过竞争性结合hsa-miR-1233-5p调控COTL1和OAS2。此外，PCR分析验证，与对照组织相比，这四个枢纽基因在OLP组织中均高表达（<0.05）。