miR‐206 inhibits cell migration through direct targeting of the actin‐binding protein Coronin 1C in triple‐negative breast cancer

摘要

Patients with triple‐negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote metastasis are desirable, in order to improve the outcome for these patients. A loss of function of a microRNA, miR‐206, is related to increased metastasis potential in breast cancers but the mechanism is not known. In this study, we show that miR‐206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin‐binding protein CORO1C, was increased. Expression of miR‐206 significantly reduced proliferation and migration while repressing CORO1C mRNA and protein levels. We demonstrate that miR‐206 interacts with the 3'‐untranslated region (3'‐UTR) of CORO1C and regulates this gene post‐transcriptionally. This post‐transcriptional regulation was dependent on two miR‐206‐binding sites within the 3'‐UTR of CORO1C and was relieved by mutations of corresponding sites. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR‐206 expression, but did not reduce proliferation. In accordance with this, overexpression of CORO1C rescued the inhibitory effect of miR‐206 on cell migration. Our findings suggest that miR‐206 represses tumor cell migration through direct targeting of CORO1C in TNBC cells which modulates the actin filaments. This pathway is a novel mechanism that offers a mechanistic basis through which the metastatic potential of TNBC tumors could be targeted.