Expression of miR-143 and miR-145 is reduced in hematopoietic stem/progenitor cells (HSPCs) of myelodysplastic syndrome patients with a deletion in the long arm of chromosome 5.
Taken together, the findings of this study indicate that miR‑143 may be a critical regulator of MDS/AML cell carcinogenesis, acting as a potent antitumour molecular target for the diagnosis or treatment of cancers associated with the abnormal expression of MLLT3/AF9, hence facilitating the development of potential therapeutics against MDS/AML.
DICER1 gene expression was lower in MSC from MDS and AML patients than HC and some differentially expressed miRNAs indicated the potential involvement of DICER1 in the pathogenesis of MDS and AML. qRT-PCR confirmation revealed down-regulated miRNAs (hsa-miR-30d-5p, hsa-miR-222-3p and hsa-miR-30a-3p in MDS; hsa-miR-1275, hsa-miR-4725-5p and hsa-miR-143-3p in AML) and over-expressed miRNAs (hsa-miR-4462 in MDS; hsa-miR-134-5p and hsa-miR-874-3p in AML) in MDS and AML.
Lenalidomide selectively abrogated progenitor activity in cells depleted of miR-143 and miR-145 supporting a key role for miR-143/145 in the sensitivity to lenalidomide of del(5q) myelodysplastic syndrome patients.