Abstract
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.