5-甲基胞嘧啶 (m5C) RNA 修饰是哺乳动物中高度丰富且重要的表观遗传修饰。作为一种重要的 RNA m5C 甲基转移酶，NOP2/Sun 结构域家族成员 2 (NSUN2) 介导的 m5C RNA 修饰在许多癌症的生物学功能调节中发挥着重要作用。然而，人们对 NSUN2 在肝细胞癌 (HCC) 中的生物学作用知之甚少。在本研究中，我们发现HCC中NSUN2的表达显着上调，且NSUN2表达较高的HCC患者比NSUN2表达较低的HCC患者预后较差。 NSUN2可以通过多种方式影响HCC的肿瘤免疫调节。体外和体内实验证实，NSUN2敲低显着降低了HCC细胞的增殖、集落形成、迁移和侵袭能力。甲基化 RNA 免疫沉淀测序 (MeRIP-seq) 显示 NSUN2 敲低显着影响 HCC 细胞中 m5C RNA 修饰的丰度、分布和组成。功能富集分析和体外实验表明NSUN2可以通过调节Wnt信号通路促进HCC细胞增殖、迁移和侵袭。通过RNA免疫沉淀测序（RIP-Seq）和MeRIP-seq鉴定SARS2为NSUN2的下游靶标，其可能在HCC中NSUN2介导的m5C RNA修饰的促肿瘤作用中发挥重要作用。总之，NSUN2 通过以 m5C 依赖性方式调节 Wnt 信号通路和 SARS2 来促进 HCC 进展。© 2024。作者，获得 Springer Nature Limited 的独家许可。

5-Methylcytosine (m5C) RNA modification is a highly abundant and important epigenetic modification in mammals. As an important RNA m5C methyltransferase, NOP2/Sun-domain family member 2 (NSUN2)-mediated m5C RNA modification plays an important role in the regulation of the biological functions in many cancers. However, little is known about the biological role of NSUN2 in hepatocellular carcinoma (HCC). In this study, we found that the expression of NSUN2 was significantly upregulated in HCC, and the HCC patients with higher expression of NSUN2 had a poorer prognosis than those with lower expression of NSUN2. NSUN2 could affect the tumor immune regulation of HCC in several ways. In vitro and in vivo experiments confirmed that NSUN2 knockdown significantly decreased the abilities of proliferation, colony formation, migration and invasion of HCC cells. The methylated RNA immunoprecipitation-sequencing (MeRIP-seq) showed NSUN2 knockdown significantly affected the abundance, distribution, and composition of m5C RNA modification in HCC cells. Functional enrichment analyses and in vitro experiments suggested that NSUN2 could promote the HCC cells to proliferate, migrate and invade by regulating Wnt signaling pathway. SARS2 were identified via the RNA immunoprecipitation-sequencing (RIP-Seq) and MeRIP-seq as downstream target of NSUN2, which may play an important role in tumor-promoting effect of NSUN2-mediated m5C RNA modification in HCC. In conclusion, NSUN2 promotes HCC progression by regulating Wnt signaling pathway and SARS2 in an m5C-dependent manner.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.