Tumor suppressor effects of miR-143 and miR-199 on the K562 myelogenous leukemia cell line by targeting the 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, a CML cell line. MiR-143 exhibited a more significant reduction in cell proliferation and invasion compared to miR-199a. Our results indicate that the overexpression of these tumor suppressor miRNAs and the subsequent downregulation of Musashi2 are responsible for reducing the cancerous properties of malignant myeloid cells, although the potential targeting of other genes by these miRNAs may contribute to these effects. Accordingly, these miRNAs could also be investigated for their effects on the behavior of cancer cells derived from clinical samples of myelogenous leukemias to evaluate their potential roles as new molecular targets in the treatment of this type of cancer.