The effect of miR-223 on cellular behaviour in non-5q myelodysplastic syndromes through targeting RPS14

Abstract

Myelodysplastic syndromes (MDS) are characterised by impaired haematopoiesis and a high risk of leukaemic transformation. A decrease in RPS14 expression in non-5q MDS patients was confirmed by immunohistochemical analyses of MDS bone marrow biopsies. To determine the cause of RPS14 reduction in non-5q MDS, we analysed the 3'-UTR of RPS14 and demonstrated that miR-223 binds to the 3'-UTR of RPS14 by bioinformatics-based approach combined with the luciferase reporter assay. Using quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significantly increased expression of miR-223 in CD34+ cells and SKM-1 cells derived from non-5q MDS patients invitro and demonstrated a correlation between miR-223 levels and red blood cell counts. Exogenous miR-223 expression in SKM-1 cells could also inhibit RPS14 expression. In functional studies, overexpression of miR-223 was shown to promote cell proliferation and inhibit cell apoptosis in SKM-1 cells, and to impair erythroid differentiation in haemin-induced K562 cells. Taken together, our results revealed that the overexpression of miR-223 in MDS is closely associated with cell transformation and erythroid differentiation arrest, which is most likely mediated by targeting RPS14.