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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