MicroRNA-134 inhibits osteosarcoma angiogenesis and proliferation by targeting the VEGFA/VEGFR1 pathway

The FEBS Journal
Long ZhangXiaojuan Sun

Abstract

Vascular endothelial growth factor (VEGF) A and vascular endothelial growth factor receptor 1 (VEGFR1) signaling is crucial for angiogenesis and progression of osteosarcoma (OS). However, the regulation of the VEGF/VEGFR1 expression is still unclear in OS. Here, we show lower levels of miRNA-134 (miR-134) in OS tissues and cells. Induction of miR-134 overexpression significantly reduced the proliferation of Saos-2 cells and their secretion of pro-angiogenic factors, but increased the frequency of apoptotic Saos-2 cells. Treatment with conditioned medium from the cells transfected with miR-134 reduced the tube formation in human umbilical vein endothelial cells, which was abrogated by a combination of VEGF and conditioned medium. Furthermore, miR-134 significantly inhibited the growth of implanted OS tumors in vivo and attenuated the VEGFA and VEGFR1 expression and angiogenesis in the tumors. In addition, higher levels of VEGFA and VEGFR1 were detected and miR-134 inhibited the expression of VEGFA and VEGFR1 in Saos-2 cells and OS tumors. Bioinformatic analysis indicated that the 3'-UTR of VEGFA and VEGFR1 contained the motif for miR-134 binding. Co-transfection with the luciferase reporter containing the wild-type, but not the ...Continue Reading

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