Inducible microRNA-200c decreases motility of breast cancer cells and reduces filamin A

可诱导的 microRNA-200c 可降低乳腺癌细胞的运动能力并降低细丝蛋白 A

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作者:Bojan Ljepoja, Christoph Schreiber, Florian A Gegenfurtner, Jonathan García-Roman, Bianca Köhler, Stefan Zahler, Joachim O Rädler, Ernst Wagner, Andreas Roidl

Abstract

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.

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