title: miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer.
abstract: 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.
authors: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, TX 77204-5506, USA.
authors: Jun
authors: J
authors: Wang
authors: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, TX 77204-5506, USA.
authors: Efrosini
authors: E
authors: Tsouko
authors: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, TX 77204-5506, USA.
authors: Philip
authors: P
authors: Jonsson
authors: Department of Oncology and Pathology, Karolinska Institutet and University Hospital, S-171 76 Stockholm, Sweden.
authors: Jonas
authors: J
authors: Bergh
authors: Department of Oncology and Pathology, Karolinska Institutet and University Hospital, S-171 76 Stockholm, Sweden.
authors: Johan
authors: J
authors: Hartman
authors: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, TX 77204-5506, USA.
authors: Eylem
authors: E
authors: Aydogdu
authors: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, TX 77204-5506, USA. Electronic address: ceciliawilliams@uh.edu.
authors: Cecilia
authors: C
authors: Williams
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; C072061:coronin proteins
keywords: Breast cancer; CORO1C; Cell migration; miR-206