OSGEP-mediated tRNA t6A modifications promotes leukaemogenesis and mediates the reistance of cytarabine in AML

Emerging research highlights the role of RNA modifications, especially tRNA modifications, in the progression of human cancers, though the molecular mechanisms remain unclear. In this study, we uncovered that OSGEP which is the tRNA N6-threonylcarbamoyladenosine (t6A) methyltransferase complex core component is significantly elevated in acute myeloid leukemia (AML) patients and correlates with poor prognosis. Impaired t6A modification upon OSGEP depletion led to decreased cell proliferation, induced cell cycle arrest, promoted apoptosis, and reduced cellular sensitivity to cytarabine. Furthermore, transcriptome and proteome profiling revealed that differentially expressed genes and proteins were enriched in cell cycle and apoptosis pathways. Our study demonstrates that OSGEP-mediated tRNA t6A modification plays a critical role in AML progression and cytarabine resistance, offering potential therapeutic targets for improving treatment outcomes in AML patients. Overall design: To investigate the role of OSGEP in AML, we first assessed the expression levels of OSGEP and tRNA t6A modification in AML cells.Then we established HL-60 cell lines in which each target gene has been knocked down by shRNA. To investigate potential pathways related to cell proliferation, cell cycle, and apoptosis, we performed transcriptome and proteome analyses of OSGEP knockdown in HL-60 cells using RNA-seq and LC-MS/MS, respectively.