Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/β-catenin signaling

摘要

MicroRNAs (miRNAs) are strongly implicated in many cancers, including breast cancer. Recently, microRNA-301a (miR-301a) has been proved to play a substantial role in gastric cancer, but its functions in the context of breast cancer remain unknown. Here we report that miR-301a was markedly upregulated in primary tumor samples from patients with distant metastases and pro-metastatic breast cancer cell lines. Gain-of-function and loss-of-function studies showed that ectopic overexpression of miR-301a promoted breast cancer cell migration, invasion and metastasis both in vitro and in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in metastatic breast cancer cells that express miR-301a, and mediated miR-301a-induced invasion and metastasis. Furthermore, miR-301a directly targeted and suppressed PTEN, one negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that miR-301a maintains constitutively activated Wnt/β-catenin signaling by directly targeting PTEN, which promotes breast cancer invasion and metastasis. Taken together, our findings reveal a new regulatory mechanism of miR-301a and suggest that miR-301a might be a potential target in breast cancer therapy.