RESUMEN
RUNX1 is a transcription factor that plays critical roles in hematopoietic proliferation and differentiation. Megakaryocyte is a precursor cell of platelets. Several reports have implied that RUNX1 is important in megakaryocytic differentiation and proliferation. However, the mechanism is not well understood. In this study, we employed a megakaryocytic cell line UT-7/GM and suppressed the RUNX1 gene expression by siRNA. Knocking down of RUNX1 induced the increase of megakaryocyte-specific gene expression and down-regulation of polyploidization. RUNX1 overexpression decreased the PF4 and GPIIb promoter activities. These results suggest that RUNX1 promotes proliferation of megakaryocytic cell line but not megakaryocytic gene expression in UT-7/GM cells.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/fisiología , Megacariocitos/metabolismo , Interferencia de ARN , Proliferación Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal/antagonistas & inhibidores , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Humanos , Megacariocitos/citología , Poliploidía , ARN Interferente Pequeño , Regulación hacia ArribaRESUMEN
The transcription factor RUNX1 plays a crucial role in hematopoiesis. RUNX1 regulates both differentiation and proliferation of hematopoietic cells. Several reports have shown that RUNX1 participates in megakaryopoiesis, which is a process that leads to formation of platelets. However, to date, the mechanisms by which this occurs have not been fully elucidated. In the present study, we investigated whether siRNA-mediated depletion of RUNX1 affected megakaryopoiesis of UT-7/GM cells. The depletion of RUNX1 in UT-7/GM cells resulted in up-regulation of the expression of megakaryocytic markers and polyploidization, while cell proliferation was down-regulated. Furthermore, the overexpression of RUNX1 decreased the activity of megakaryocytic gene promoters. These results suggest that RUNX1 down-regulates terminal differentiation of megakaryocytes and promotes proliferation of megakaryocytic progenitors.