The role of m5C RNA methylation regulators in the diagnosis and immune microenvironment of osteoarthritis

The 5-methylcytosine (m5C) is a common post-transcriptional RNA methylation modification and is involved in the pathological process of many diseases. However, little is known about the role of m5C in osteoarthritis (OA). OA gene data and the corresponding information were downloaded from the Gene Expression Omnibus database. Based on 36 m5C regulators, we constructed the landscape and diagnostic model for OA. Later, two m5C modification patterns were identified, and functional analyses were performed to evaluate whether these patterns were related to endoplasmic reticulum (ER) stress and mitochondrial autophagy. We further comprehensively analyzed the immune cell infiltration characteristics in different modification patterns in OA. We also established the post-transcriptional regulatory networks and drug-gene networks. Our findings suggested that m5C regulators were differentially expressed between OA and normal samples and could serve as novel biomarkers for the diagnosis of OA. Besides, m5C regulators may be involved in regulating ER stress, mitochondrial autophagy, and immune infiltration in OA. The m5C modification can influence the sensitivity to drugs and the potential post-transcriptional regulatory mechanisms might provide promising targets.

5-甲基胞嘧啶（5-methylcytosine, m5C）是一类常见的转录后RNA甲基化修饰，参与多种疾病的病理进程。然而，目前关于m5C在骨关节炎（osteoarthritis, OA）中的作用仍鲜有研究。本研究从基因表达综合数据库（Gene Expression Omnibus, GEO）下载了OA相关基因数据集及对应注释信息。基于36个m5C调控因子，我们构建了OA的修饰调控图谱与诊断模型。随后我们鉴定出两种m5C修饰模式，并通过功能分析验证了这些模式与内质网（endoplasmic reticulum, ER）应激及线粒体自噬（mitochondrial autophagy）的相关性。我们进一步全面分析了OA不同修饰模式下的免疫细胞浸润特征，同时构建了转录后调控网络与药物-基因调控网络。本研究结果显示，m5C调控因子在OA样本与正常对照样本中存在差异表达，可作为OA诊断的新型生物标志物。此外，m5C调控因子可能参与调控OA中的内质网应激、线粒体自噬及免疫浸润过程。m5C修饰可影响药物敏感性，其潜在的转录后调控机制有望成为颇具前景的治疗靶点。