HDAC2-miR183-5p Epigenetic Circuit Contributes to the Growth of Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia via PTEN/AKT and c-MYC Signaling Pathway

Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph(+)B-ALL) is a hematological malignancy with a poor prognosis. Epigenetic abnormalities, especially abnormal histone acetylation and microRNAs (miRNAs) dysregulation, are a group of epigenetic patterns that contribute to leukemia progression. However, their regulatory mechanisms in Ph(+)B-ALL have not been fully elucidated. In this study, we identified that miR-183-5p is significantly downregulated in Ph(+)B-ALL and associated with poor prognosis. Moreover, we found that the BCR-ABL fusion gene is a key target gene of miR-183-5p. MiR-183-5p directly targets BCR-ABL gene and induces cell apoptosis via PTEN/AKT and c-MYC signaling pathways. In addition, histone deacetylase inhibitor (HADCi) could mitigate the suppressive effects of HDAC2 on miR-183-5p by promoting promoter acetylation, thereby enhancing cell apoptosis. In conclusion, our results indicate that miR-183-5p is a potential biomarker and suggest that a novel "HDAC2-miR-183-5p epigenetic circuitry regulation" may be involved in the pathogenesis of Ph(+)B-ALL. Taken together, These findings provide new insights into the design of promising molecular-targeted drugs for Ph(+)B-ALL.