MicroRNA dysregulation in mesenchymal stromal cells in myelodysplastic syndromes and its modulation by azacitidine and bortezomib

Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem and progenitor cells characterized by ineffective hematopoiesis, bone marrow dysplasia and variable progression to acute myeloid leukemia. Mesenchymal stromal cells (MSCs) contribute to MDS pathogenesis through mechanisms partly mediated by microRNAs (miRNAs). We characterized the miRNA profile of MDS-derived MSCs and evaluated its modulation by 5-azacitidine (5-AZA) and bortezomib (BTZ). Small RNA sequencing and RT-qPCR identified significant downregulation of miR-20a-5p in MDS-MSCs, while 5-AZA restored its expression to control levels. Reduced miR-20a-5p was also detected in plasma from MDS patients, supporting its biomarker potential. BTZ induced a marked 5-6-fold upregulation of miR-192-5p in patient- and control-derived MSCs. Functional enrichment analyses linked dysregulated miRNAs to extracellular matrix organization, inflammatory signaling and epigenetic regulation, supporting their role in MSC dysfunction. These findings identify stromal miRNAs as potential biomarkers and therapeutic targets in MDS.