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

Abstract

Muyang Zhang,1,&ast; Limin Miao,2,&ast; Huyan Chen,3 Hongying Sun,1 Qiaozhen Yang1 1Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Geriatric Dentistry, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaozhen Yang, Department of Stomatology, Huashan Hospital Affiliated to Fudan University, No. 12, Middle Wulumuqi Road, Jing’an District, Shanghai, 200040, People’s Republic of China, Tel [phone], Email [email protected] Hongying Sun, Department of Stomatology, Huashan Hospital Affiliated to Fudan University, No. 12, Middle Wulumuqi Road, Jing’an District, Shanghai, 200040, People’s Republic of China, Tel [phone], Email [email protected]: 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 (P < 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.Keywords: oral lichen planus, competing endogenous RNAs, weighted gene co-expression network analysis, non-coding RNAs

Keywords

• Oral lichen planus
• competing endogenous RNAs
• Weighted gene co-expression network analysis
• non-coding RNAs