miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer
2014 (English)In: Molecular oncology, ISSN 1878-0261, Vol. 8, no 8, 1690-702 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 8, no 8, 1690-702 p.
Cell and Molecular Biology
Research subject SRA - Molecular Bioscience
IdentifiersURN: urn:nbn:se:kth:diva-165342DOI: 10.1016/j.molonc.2014.07.006ISI: 000346215200026PubMedID: 25074552ScopusID: 2-s2.0-84911966142OAI: oai:DiVA.org:kth-165342DiVA: diva2:808100
QC 201504272015-04-272015-04-272015-04-27Bibliographically approved