Tumor suppressor effects of miR-143 and miR-199 on myelogenous leukemia cells through targeting RNA-binding protein Musashi2

The RNA-binding protein Musashi2 plays a critical role in normal and malignant hematopoiesis. Aberrant expression of Musashi2 is linked to the inappropriate expression of several miRNAs. In this study, we observed downregulation of miR-143 and miR-199 in CML and AML cell lines. Bioinformatic analysis revealed potential interactions between these miRNAs and Musashi2 mRNA, which were also confirmed by our experimental data. In K562 cells, which showed the strongest negative correlation between Musashi2 and the candidate miRNAs, overexpression of miRNAs led to reduced cell proliferation and invasiveness. Overexpression of miR-143 and miR-199 decreased the mRNA and protein levels of Musashi2 in K562 cells, with miR-143 showing a more significant reduction in cell proliferation and invasion compared to miR-199a. Our results indicate that the downregulation of Musashi2 following the overexpression of these tumor suppressor miRNAs is responsible for diminishing the cancerous properties of malignant myeloid cells. According to our findings, these miRNAs could be new potential molecular targets for the treatment of myelogenous leukemias.