Zhang Rong, Liu Zhuogang, Zhang Guojun
Department of Hematology, Shenjing Hospital of China Medical University Shenyang, Liaoning Province, People's Republic of China.
Am J Transl Res. 2021 Sep 15;13(9):10218-10232. eCollection 2021.
Acute myeloid leukemia (AML) is a heterogenous hematologic disease that has a poor prognosis. This study aimed to identify new targets for the diagnosis and treatment of AML. The GSE65409 and GSE90062 were selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to identify differentially expressed genes (DEGs). The Database for Annotation, Visualization, and Integrated Discovery was used to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the DEGs. Protein-protein interactions were visualized using the Search Tool for the Retrieval of Interacting Genes, which identified two potential hub genes that encode CDC45 and MCM7. Relative to AML specimens, normal specimens had higher expression levels of CDC45 and MCM7 based on the Gene Expression Omnibus and The Cancer Genome Atlas databases. Furthermore, Pearson's correlation analysis revealed a significant relationship between CDC45 and MCM7. High expression of CDC45 was positively correlated with complete remission and negatively correlated with white blood cell count, hemoglobin concentration, platelet count, and bone marrow blasts. Moreover, high expression of MCM7 was negatively correlated with white blood cell count, hemoglobin concentration, platelet count, bone marrow blasts, and unfavorable cytogenetics. Overexpression of CDC45 increased the expressions of CDC45 and MCM7, while overexpression of MCM7 increased the expression of MCM7 but not CDC45. Overexpression of CDC45 or MCM7 led to impaired AML cell proliferation and blockage at the G1/S phase transition. Overexpression of CDC45 or MCM7 also attenuated the phosphorylation of PI3K, AKT, and mTOR, while simultaneous down-regulation of MCM7 expression abolished the effects of CDC45 overexpression. These findings suggest a functional relationship between CDC45 and MCM7, which might have use in the diagnosis and treatment of AML.
急性髓系白血病（AML）是一种预后较差的异质性血液系统疾病。本研究旨在确定AML诊断和治疗的新靶点。从基因表达综合数据库的AML数据库中选取GSE65409和GSE90062，并使用GEO2R工具进行比较，以鉴定差异表达基因（DEG）。利用注释、可视化和综合发现数据库对DEG进行基因本体论和京都基因与基因组百科全书分析。使用检索相互作用基因的搜索工具对蛋白质-蛋白质相互作用进行可视化，该工具鉴定出两个潜在的枢纽基因，它们编码CDC45和MCM7。基于基因表达综合数据库和癌症基因组图谱数据库，相对于AML标本，正常标本中CDC45和MCM7的表达水平更高。此外，Pearson相关性分析显示CDC45和MCM7之间存在显著关系。CDC45的高表达与完全缓解呈正相关，与白细胞计数、血红蛋白浓度、血小板计数和骨髓原始细胞呈负相关。此外，MCM7的高表达与白细胞计数、血红蛋白浓度、血小板计数、骨髓原始细胞和不良细胞遗传学呈负相关。CDC45的过表达增加了CDC45和MCM7的表达，而MCM7的过表达增加了MCM7的表达，但未增加CDC45的表达。CDC45或MCM7的过表达导致AML细胞增殖受损，并在G1/S期转换时受阻。CDC45或MCM7的过表达还减弱了PI3K、AKT和mTOR的磷酸化，而同时下调MCM7的表达则消除了CDC45过表达的作用。这些发现表明CDC45和MCM7之间存在功能关系，这可能在AML的诊断和治疗中具有应用价值。
