Abstract: Objective 5-methylcytosine （m5C） modification of RNA is involved in a variety of physiological and pathological processes, especially in the occurrence and development of tumors. In this study, the relationship between the level of m5C in pan-cancer and prognosis was analyzed by m5C modified regulatory genes, and the potential m5C inhibitory were explored. Methods the RNA-Seq data of 33 cancers were downloaded from the cancer gene map （TCGA） database, and the expression levels of M5C regulatory genes in cancer and paracancerous tissues were analyzed by R software. Then, we predicted the potential drugs that might inhibit m5C modification in pan-cancer by The Connectivity Map （CMap）, and verified their inhibitory effects by the m5C dot blot and cell viability assay. Results In most tumor types, Writers and Readers of m5C were significantly overexpressed. The overall survival times （OS） of patients with high level of m5C was significantly shorter than that of patients with low level of m5C. Importantly, the predicted m5C inhibiting drugs can effectively inhibit the total m5C level and proliferation of cancer cells. Conclusion Our study shows that in many types of cancers, the high level of m5C modification and the abnormal expression of m5C regulatory molecules are closely related to malignant tumors, indicating that m5C modification regulators may be promising biomarkers for prognosis. and can be used as valuable targets for cancer treatment.

Key words: 5-methylcytosine modification, pan-cancer, prognosis, m5C inhibitor

摘要： 目的 RNA的5-甲基胞嘧啶（m5C）修饰参与多种生理和病理过程,特别是在肿瘤的发生和发展中。本研究通过泛癌中m5C修饰调节因子分析泛癌中的m5C水平与预后的关系,并探究潜在的m5C抑制药物。方法 从癌症基因图谱（TCGA）数据库下载33种癌症的RNA-Seq数据,使用R软件分析m5C修饰调节因子在癌和癌旁组织中的表达水平。随后,我们通过CMap预测可能抑制泛癌中m5C修饰的潜在药物,并通过m5C dot blot和细胞生长实验验证其抑制作用。结果 在大多数肿瘤类型中,m5C的Writers和Readers都有着明显的高表达,肿瘤组织m5C总体水平高的相较于m5C总体水平低的患者,其总体生存期（OS）显著缩短（P<0.05）。重要的是,预测的m5C抑制药物可以有效抑制癌细胞的总体m5C水平以及增殖。结论 我们的研究表明,在多种癌症类型中,高水平的m5C修饰和m5C修饰调节因子的异常表达与恶性肿瘤密切相关,表明m5C修饰调节因子可能是有希望的预后生物标志物,并可作为癌症治疗的潜在靶点。

关键词: m5C修饰, 泛癌, 预后, m5C抑制剂