IDH1作为非经典RNA结合蛋白维持急性髓系白血病细胞系HL-60的分化阻滞OA

Objective To investigate the novel mechanism by which isocitrate dehydrogenase 1(IDH1)suppresses differentiation in acute myeloid leukemia(AML)HL-60 cells.Methods Potential RNA-binding proteins were ini-tially screened through literature review and database analyses,leading to the selection of IDH1 as the candidate of interest.RNA immunoprecipitation followed by sequencing(RIP-seq)was performed to identify RNAs bound by IDH1 in HL-60 cells.In parallel,IDH1 was knocked down via lentiviral transduction,and transcriptome profiling was conducted by RNA sequencing(RNA-seq)to assess global gene expression changes induced by IDH1 depletion.Integrated analysis of RIP-seq and RNA-seq data was further carried out to systematically characterize the expression patterns of IDH1-bound transcripts following IDH1 knockdown.Results IDH1 was found to bind a broad spectrum of RNA molecules in HL-60 cells,with mRNAs representing the predominant class.Knockdown of IDH1 resulted in marked alterations in the cellular gene expression profile.Integrated analysis revealed that IDH1-bound transcripts exhibited an overall downregulation upon IDH1 depletion and were significantly enriched in genes associated with differentiation blockade in leukemic cells.Conclusions IDH1 functions as a non-canonical RNA-binding protein that participates in the regulation of differentiation-associated genes in AML,thereby contributing to the maintenance of the undifferentiated state of leukemia cells.