RNA m?C甲基转移酶NSUN1促进急性髓系白血病细胞生长的研究

Objectives: Acute Myeloid Leukemia (AML) is a highly aggressive and heterogeneous hematological malignancy with a median age of 68 years. Despite the existence of standard chemotherapy methods such as "7+3" regimen, elderly patients have poor tolerance, and the overall 5-year survival rate is still less than 30%, even less than 5% in the elderly. Although a variety of targeted drugs have been approved in recent years, the treatment options for relapsed/refractory AML are still limited. Therefore, in-depth understanding of the pathogenic mechanism of AML is of great significance for optimizing the treatment strategy. NSUN1, a member of the RNA m?C methyltransferase family, has been shown to have potential oncogenic functions in some solid tumors, but its role in AML remains unclear. The aim of this study is to systematically evaluate the function of NSUN1 in AML progression and to preliminarily analyze its possible molecular mechanism. Methods: (1) TCGA and GEPIA databases were used to analyze the expression level of NSUN1 in patients with acute myeloid leukemia (AML). At the same time, CD34? cells from normal bone marrow and AML patients were collected and combined with AML cell lines to detect the specific expression of NSUN1. (2) Lentivirus-mediated delivery of specific shRNA targeting NSUN1 to THP-1 and MOLM-13 cells was used to detect the changes in cell proliferation, colony formation, andapoptosis after NSUN1 silencing. (3) RNA-Seq was performed on MOLM-13 cells with NSUN1 knockdown, GSEA enrichment analysis of differential genes were performed. Some differentially expressed genes were selected for expression verification by RT-qPCR. Results: (1) Based on TCGA and GEPIA database analysis results, NSUN1 was significantly overexpressed in a variety of tumors, including acute myeloid leukemia (AML), and its high expression was closely related to poor prognosis. Clinical samples further confirmed that the expression of NSUN1 in CD34? cells of AML patients was significantly higher than that in CD34? cells of normal bone marrow. (2) Knockdown of NSUN1 in THP-1 and MOLM-13 cells significantly inhibited cell proliferation and colony formation, while significantly increased the proportion of cell apoptosis. (4) GSEA analysis of RNA-seq data showed that silencing NSUN1 significantly enriched tumor-related pathways. Some differentially expressed genes were selected for verification, and the experimental results were consistent with the suggestions of RNA-seq data. Among them, silencing of NSUN1 significantly enhanced the expression of BAX, a key pro-apoptotic gene.