Decitabine induces cell differentiation and growth inhibition accompanied by upregulation of microRNA‑143 and MS4A3 in the myelodysplastic syndromes‑derived leukemic cell line MDS‑L

Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis and cytopenia. Hypomethylating agents (HMAs) serve a central role in the treatment of high‑risk MDS, but their mechanisms of action are diverse and not fully understood. To investigate the molecular mechanisms of HMAs, an MDS cell line (MDS‑L) was cultured with a non‑toxic concentration of decitabine (DAC) for 6 months and drug sensitivity, cell differentiation and DNA methylation profiles were evaluated. MDS‑L cells with long‑term exposure to DAC (MDS‑L‑DAC) were morphologically mature with nuclear lobulation and cytoplasmic granulation, accompanied by decreased expression levels of the CD34 surface antigen. MDS‑L‑DAC cells exhibited decreased Wilms tumor 1 (WT1) expression levels and increased induction of apoptosis by DAC. DNA methylation array analysis demonstrated the demethylation of membrane spanning 4‑domains A3 (MS4A3) and microRNA‑143 (miR143) in MDS‑L‑DAC cells. miR143 functions as a tumor suppressor through the MAPK/ERK pathway, and in MDS‑L‑DAC cells, decreased expression levels of KRAS and β‑catenin were observed, associated with the increased expression of miR143. The differentiation of MDS cells and decreased expression levels of WT1 induced by long‑term incubation with DAC may involve the restoration of function via demethylation of the miR143 and MS4A3 gene promoters, which could potentially contribute to eliminating the malignant phenotype through reductions in KRAS and β‑catenin expression levels.