miR-205 targets angiogenesis and EMT concurrently in anaplastic thyroid carcinoma

Abstract

The current study aims to evaluate for the first time the inhibitory roles of miR-205 in the pathogenesis of anaplastic thyroid carcinoma. In addition, we investigated the mechanisms by which miR-205 regulates angiogenesis and epithelial-to-mesenchymal transition (EMT) in cancer. Two anaplastic thyroid carcinoma cell lines were transfected with the expression vector pCMV-MIR-205. Selected markers of angiogenesis and EMT including vascular endothelial growth factor A (VEGF-A) and zinc finger E-box-binding homeobox 1 (ZEB1) were investigated by Western blot. The interaction of miR-205 expression with EMT and angiogenesis were also investigated by assessment of matrix metalloproteinases 2 and 9 (MMP2 and MMP 9), SNAI1 (Snai1 family zinc finger 1), vimentin, E-cadherin and N-cadherin. The function of miR-205 was further tested with VEGF enzyme-linked immunosorbent assay (ELISA), wound healing, invasion and tube formation assays. Using an animal model, we studied the association of miR-205 with angiogenesis, proliferation and invasion. The following results were obtained. Permanent overexpression of miR-205 significantly suppressed angiogenesis and EMT by simultaneously targeting VEGF-A, ZEB1 and downstream products. Ectopic expression of miR-205 in cancer cells led to decreased migration, invasion and tube formation of endothelial cells. In addition, inhibition of tumour growth, vascularisation and invasion were noted in the mouse tumour xenografts. Our findings provide insights into simultaneous regulatory role of miR-205 in the pathogenesis of anaplastic thyroid carcinoma by suppressing both angiogenesis and EMT. This may open avenues to exploit miR-205 as an alternative cancer therapeutic strategy in the future.