Zheng Haishi, Aihaiti Yirixiati, Cai Yongsong, Yuan Qiling, Yang Mingyi, Li Zheng, Xu Ke, Xu Peng
Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, People's Republic of China.
J Inflamm Res. 2023 Nov 1;16:5001-5025. doi: 10.2147/JIR.S431076. eCollection 2023.
The goal of this study was to explore the expression characteristics of RNA modification-related genes, reveal immune landscapes and identify novel potential diagnostic biomarkers in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.
RNA microarray and single-cell sequencing (scRNA-seq) data were downloaded from gene expression omnibus (GEO) database. Differentially expressed RNA modification-related genes were identified and then functionally annotated. Univariate logistic regression and lasso regression analysis were used to identify primary disease genes for OA and RA. Validation was done using scRNA-seq analysis and immunohistochemistry (IHC) in human knee synovial tissues and a murine destabilization of the medial meniscus (DMM) model. Through WGCNA analysis, genes associated with cell pyroptosis or autophagy in OA and RA were identified, which were then combined with differentially expressed RNA modification-related genes to construct a PPI interaction network. Furthermore, hub genes were selected for ceRNA interaction network analysis, correlation analysis with OA and RA molecular subtypes, as well as correlation analysis with 22 immune cells.
Six RNA modification-related genes ( and ) were identified as potential OA and RA pathogenesis biomarkers. Their expression was validated in human knee synovial tissues and a murine DMM model. Functional enrichment of differentially expressed RNA modification-related genes between RA and OA was analyzed using GO, KEGG, GSEA, and GSVA. Based on WGCNA and PPI analysis, the six hub genes related to pyroptosis and RNA modification (, and ) were identified as central nodes for ceRNA interaction, correlation with OA and RA molecular subtypes, and association with 22 immune cells.
Our research revealed the significance of RNA modification-related genes in the development of OA and RA pathogenesis, thereby providing a novel research direction for understanding the mechanisms, diagnosis, and treatment of OA and RA.
本研究的目的是探讨RNA修饰相关基因的表达特征，揭示骨关节炎（OA）和类风湿关节炎（RA）患者的免疫图谱，并鉴定新的潜在诊断生物标志物。
从基因表达综合数据库（GEO）下载RNA微阵列和单细胞测序（scRNA-seq）数据。鉴定差异表达的RNA修饰相关基因，然后进行功能注释。采用单变量逻辑回归和套索回归分析鉴定OA和RA的原发性疾病基因。在人膝关节滑膜组织和小鼠内侧半月板不稳定（DMM）模型中，通过scRNA-seq分析和免疫组织化学（IHC）进行验证。通过加权基因共表达网络分析（WGCNA），鉴定出与OA和RA中细胞焦亡或自噬相关的基因，然后将其与差异表达的RNA修饰相关基因结合，构建蛋白质-蛋白质相互作用（PPI）网络。此外，选择枢纽基因进行竞争性内源性RNA（ceRNA）相互作用网络分析、与OA和RA分子亚型的相关性分析，以及与22种免疫细胞的相关性分析。
六个RNA修饰相关基因（……）被鉴定为潜在的OA和RA发病机制生物标志物。它们的表达在人膝关节滑膜组织和小鼠DMM模型中得到验证。使用基因本体论（GO）、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）和基因集变异分析（GSVA）分析RA和OA之间差异表达的RNA修饰相关基因的功能富集情况。基于WGCNA和PPI分析，鉴定出与焦亡和RNA修饰相关的六个枢纽基因（……）作为ceRNA相互作用、与OA和RA分子亚型相关性以及与22种免疫细胞相关性的中心节点。
我们的研究揭示了RNA修饰相关基因在OA和RA发病机制发展中的重要性，从而为理解OA和RA的机制、诊断和治疗提供了新的研究方向。
