MicroRNA-139-5p/Flt1/Wnt/β-catenin regulatory crosstalk modulates the progression of glioma

Fms-related tyrosine kinase 1 (Flt1), the receptor of VEGF/PIGF, is associated with cancer angiogenesis and tumorigenesis. Although the high expression of Flt1 in glioma is identified, its regulatory mechanism remains unclear. In the present study, we demonstrate that miR-139-5p inhibits Flt1 expression mediated by binding its 3′ untranslated region (3′UTR) to regulate the progression of human glioma. We found miR-139-5p was downregulated in glioma tissues compared with normal brain tissues whereas a converse expression level of Flt1 was observed. Additionally we proved that miR-139-5p directly integrated with the 3′UTR of Flt1 via luciferase activity assay and cells transfected with miR-139-5p characterized with a low expression of Flt1 in mRNA and protein levels. Furthermore, we validated that miR-139-5p enforced its biological modulation via targeting Flt1 through rescue experiments. miR-139-5p suppressed and Flt1 stimulated the malignant activities of glioma cells. We demonstrated that miR-139-5p inhibited the Flt1-mediated Wnt/β-catenin signaling pathway in glioma cells. Conclusively, our study indicated that miR-139-5p can counteract the malignant phenotypes of glioma cells by the inhibitory effect of the Flt1-mediated Wnt/β-catenin signaling pathway.