The potential role of BM-MSC-derived exosomes in TUG1 modulation: antileukemic effects on THP-1 cells.

Mesenchymal stem cell-derived exosomes (BM-MSC-Exos) have attracted increasing interest for their potential to modulate leukemic cell behavior in acute myeloid leukemia (AML). In this study, the effects of BM-MSC-Exos on the AML cell line THP-1 were evaluated. A dose-dependent reduction in cell viability was observed after 24 h of treatment, as determined by MTT assay. Flow-cytometric analysis revealed a significant increase in apoptotic activity following exposure to BM-MSC-Exos. Cell cycle analysis demonstrated an accumulation of cells in the G0/G1 phase, consistent with growth arrest. Gene-expression profiling by real-time PCR showed upregulation of pro-apoptotic genes (Caspase3, Caspase9, BID, and BAX) and downregulation of the anti-apoptotic gene BCL2. Likewise, expression of cell cycle regulators such as Cyclin D1 and CDK6 was reduced. Importantly, TUG1, an oncogenic long non-coding RNA implicated in leukemogenesis, was also significantly downregulated in exosome-treated cells. Taken together, these results may shed light on the possible role of BM-MSC-Exos in regulating apoptosis, cell-cycle progression, and TUG1 expression in leukemic cells. Further studies are warranted to elucidate the molecular mechanisms underlying these effects and to determine how BM-MSC-Exos-mediated modulation of TUG1 might contribute to leukemic cell regulation.