NSUN2根据M5C RNA的修饰调节Wnt信号通路，以促进肝细胞癌的进展
NSUN2 regulates Wnt signaling pathway depending on the m5C RNA modification to promote the progression of hepatocellular carcinoma
影响因子:7.30000
分区:医学1区 Top / 生化与分子生物学1区 遗传学1区 细胞生物学2区 肿瘤学2区
发表日期:2024 Nov
作者:
Huiwu Xing, Xinyu Gu, Yingru Liu, Lixia Xu, Yuting He, Chen Xue
摘要
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。作为重要的RNA M5C甲基转移酶，NOP2/太阳域家族成员2（NSUN2）介导的M5C RNA修饰在许多癌症的生物学功能的调节中起重要作用。但是，对于NSUN2在肝细胞癌（HCC）中的生物学作用知之甚少。在这项研究中，我们发现NSUN2的表达在HCC中显着上调，并且NSUN2表达较高的HCC患者的预后较差，而NSUN2表达较低。 NSUN2可能会以多种方式影响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，菌落形成，迁移和侵袭的能力。甲基化的RNA免疫沉淀 - 测序（Merip-Seq）显示NSUN2敲低显着影响了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信号通路来促进HCC细胞以增殖，迁移和入侵。通过RNA免疫沉淀 - 测序（RIP-SEQ）和MERIP-SEQ作为NSUN2的下游靶标鉴定了SARS2，这可能在HCC中NSUN2介导的M5C RNA修饰的肿瘤促进作用中起重要作用。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的进程。
Abstract
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.