MiR‑30a inhibits epithelial‑mesenchymal transition and metastasis in triple‑negative breast cancer by targeting ROR1.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. In the present study, we revealed that the expression of miR-30a was significantly decreased in TNBC, and TNBC patients with low expression of miR-30a were associated with high histological grade and more lymph node metastasis. Moreover, we found that miR-30a suppressed TNBC cell epithelial-mesenchymal transition (EMT), as demonstrated by the overexpression of miR-30a which increased the expression of epithelial marker E-cadherin but decreased the expression of mesenchymal markers N-cadherin and vimentin. Furthermore, we demonstrated that overexpression of miR-30a significantly suppressed TNBC cell invasion and migration, as well as inhibited tumor growth and metastasis in vivo. More importantly, RTK-like orphan receptor 1 (ROR1) was predicted as the direct target of miR-30a, which was subsequently confirmed by luciferase assays. Forced expression of miR-30a in TNBC cells decreased ROR1 expression, whereas the overexpression of ROR1 reversed the suppressive effects of miR-30a in TNBC cell migration and invasion. Collectively, this study indicated that miR-30a functions as a tumor-metastasis suppressor miRNA in TNBC by directly targeting ROR1 and that miR-30a may serve as a novel therapeutic target for TNBC.