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


Autoři: Bojan Ljepoja aff001;  Christoph Schreiber aff002;  Florian A. Gegenfurtner aff003;  Jonathan García-Roman aff001;  Bianca Köhler aff001;  Stefan Zahler aff003;  Joachim O. Rädler aff002;  Ernst Wagner aff001;  Andreas Roidl aff001
Působiště autorů: Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany aff001;  Faculty of Physics and Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany aff002;  Pharmaceutical Biology, Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224314

Souhrn

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.

Klíčová slova:

Breast cancer – Cancer cell migration – Cell motility – Doxycycline – Metastasis – MicroRNAs – Transcription factors – Transcriptional control


Zdroje

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