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.