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Ljepoja, Bojan; Schreiber, Christoph; Gegenfurtner, Florian A.; Garcia-Roman, Jonathan; Köhler, Bianca; Zahler, Stefan; Raedler, Joachim O.; Wagner, Ernst; Roidl, Andreas (2019): Inducible microRNA-200c decreases motility of breast cancer cells and reduces filamin A.
In: PLOS One 14(11), e0224314
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Cancer progression and metastases are frequently related to changes of cell motility. Amongst others, the microRNA-200c (miR-200c) was shown to maintain the epithelial state of cells and to hamper migration. Here, we describe two miR-200c inducible breast cancer cell lines, derived from miR-200c knock-out MCF7 cells as well as from the miR-200c-negative MDA-MB-231 cells and report on the emerging phenotypic effects after miR-200s induction. The induction of miR-200c expression seems to effect a rapid reduction of cell motility, as determined by 1D microlane migration assays. Sustained expression of miR200c leads to a changed morphology and reveals a novel mechanism by which miR- 200c interferes with cytoskeletal components. We find that filamin A expression is attenuated by miRNA-200c induced downregulation of the transcription factors c-Jun and MRTF/SRF. This potentially novel pathway that is independent of the prominent ZEB axis could lead to a broader understanding of the role that miR200c plays in cancer metastasis.