miR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1α

Abstract

Angiogenesis is a key factor in the growth and dissemination of malignant diseases, including breast cancer, with significant implications for its clinical management. It is known that microRNAs (miRNAs) play important roles in regulating tumor properties in cancers. However, whether miR-497 contributes to breast cancer angiogenesis remains unknown. Our study demonstrated that miR-497 was significantly downregulated in breast cancer tissue samples and cell lines. Conditioned medium obtained from breast cancer cell line MCF-7, treated with miR-497 mimics, suppressed the proliferation and tube formation of human umbilical vein endothelial cells in vitro, in comparison with the untransfected cells or cells transfected with the control vector alone. Furthermore, western blot assay confirmed that the overexpression of miR-497 reduced VEGF and HIF-1α protein levels. In addition, stable transfection of miR-497 inhibited tumorigenicity and angiogenesis in vivo. Moreover, HIF-1α was also increased in the breast cancer cells under a hypoxic condition, while the ectopic expression of miR-497 partially restored its level. Taken together, our findings indicate that miR-497 is a potential target for the biological therapy of breast cancer. Moreover, miR-497 inhibited the growth of tumors and reduced angiogenesis in a nude mouse xenograft tumor model, which was probably caused by the downregulation of pro-angiogenic molecules, such as VEGF and HIF-1α.