Disulfidptosis and Its Impact on Acute Myeloid Leukemia: A Study of Gene Expression and miRNA Interactions

Acute myeloid leukemia (AML) is a rapidly progressing cancer that significantly affects myeloid blood cell lineages, presenting considerable treatment challenges and resulting in poor prognosis despite advancements in therapy. This study investigates disulfidptosis, a type of cell death triggered by disulfide stress and characterized by the accumulation of disulfide bonds, specifically in the context of AML development. The research focuses on variations in the expression of disulfidptosis-related genes (DRGs) and their associated microRNAs (miRNAs) among AML patients with the goal of identifying novel targets that could be exploited to improve treatment outcomes and diagnostic tools for AML patients. Materials and Methods: Firstly, AML-related differentially expressed genes were extracted from the TCGA database using the Gene Expression Profiling Interactive Analysis (GEPIA۲) tool to detect differentially expressed DRGs. Then, we identified microRNAs (miRNAs) that specifically target the DRGs using the miRTarBase database. Finally, the miRNA-mRNA regulatory network was subjected to pathway enrichment analysis using the NcPath tool to assess the functions and pathway enrichment related to these genes. Results: A total of nine differentially expressed DRGs, including DSTN, NCKAP۱, MYH۹, GYS۱, MYH۱۰, SLC۷A۱۱, OXSM, SLC۳A۲, and NDUFA۱۱ were defined in AML patients. We also detected four experimentally validated miRNAs (hsa-miR-۳۴c-۳p, hsa-miR-۱۲۲-۵p, hsa-miR-۲۰۰a-۳p, and hsa-miR-۱۲۲-۵p) specifically target DRGs. Remarkably, the mRNAs-miRNAs network was significantly enriched in the sphingolipid signaling, adherens junction, focal adhesion, Hippo, JAK-STAT, and mTOR signaling pathways Conclusion: This study highlights the significant role of disulfidptosis in acute myeloid leukemia (AML) and its potential as a therapeutic target. Key disulfidptosis-related genes and their regulatory miRNAs were identified, revealing how disulfide bond accumulation leads to cell death in AML. The enrichment of the miRNA-mRNA network in pathways such as the sphingolipid signaling pathway suggests new molecular targets for treatment. These insights may pave the way for innovative diagnostic tools and therapeutic strategies to enhance AML patient outcomes.

کلیدواژه ها:

AML ، Cell death ، Disulfidoptosis ، miRNA