BCOR Mutation Induces the Change of Cell Biological Behaviors in Myelodysplastic Syndromes via PI3K/Akt/mTOR Pathway
Objective To explore the molecular mechanism of BCL6 co-repressor(BCOR)gene mutation in mediating the cell bi-ological behaviors of myelodysplastic syndromes(MDS).Methods K562 cells were transfected with BCORP483L expression lentivirus and empty vector virus,respectively.Colony formation test was used to detect the effect of BCORP483L mutation on the clonogenic formation a-bility of cells.The cell apoptosis and cell cycle were analyzed by flow cytometry.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of pyroptosis and PI3K/Akt/mTOR pathway.And RNA-Sequencing(RNA-Seq)was used to detect the effect of BCORP483L mutation on the expressions of downstream target genes.Results BCORP483L mutation sig-nificantly inhibited the colony formation ability of cells,promoted cell apoptosis,blocked the cell cycle,and increased pyroptosis.RNA-Seq analysis showed that the genes related to cell apoptosis,G2M cycle checkpoint,chronic myeloid leukemia,cell senescence,intracel-lular inflammatory response,and the target genes of oncogene MYC were up-regulated in the K562 cells after BCORP483L mutation.West-ern blot experiment further confirmed that BCORP483L mutation significantly inhibited the PI3K/Akt/mTOR pathway in the K562 cells.Conclusion BCORP483L mutation promotes cell apoptosis and inhibits cell proliferation via the inhibition of PI3K/Akt/mTOR pathway.And BCORP483L mutation can up-regulate the cell-senescence-related genes,oncogene MYC target genes,and increases the level of the intracellular inflammatory response,thus promoting the development of MDS.
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