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miR-206 inhibits ce...
miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer
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- Wang, Jun (författare)
- University of Houston, United States
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- Tsouko, Efrosini (författare)
- University of Houston, United States
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- Jonsson, Philip (författare)
- University of Houston, United States
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- Bergh, Jonas (författare)
- Karolinska Institutet
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- Hartman, Johan (författare)
- Karolinska Institutet
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- Aydogdu, Eylem (författare)
- University of Houston, United States
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- Williams, Cecilia, 1969- (författare)
- University of Houston, United States
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(creator_code:org_t)
- 2014-07-12
- 2014
- Engelska.
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Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 8:8, s. 1690-702
- Relaterad länk:
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https://febs.onlinel...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- SRA - Molecular Bioscience
- SRA - Molekylär biovetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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