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

• Published in: PloS one Vol. 14; no. 11; p. e0224314
• Main Authors: Ljepoja, Bojan, Schreiber, Christoph, Gegenfurtner, Florian A, García-Roman, Jonathan, Köhler, Bianca, Zahler, Stefan, Rädler, Joachim O, Wagner, Ernst, Roidl, Andreas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-11-2019; Public Library of Science (PLoS)
• Subjects: Antibiotics; Biology and Life Sciences; Breast cancer; Breast Neoplasms - genetics; c-Jun protein; Cancer cells; Cancer metastasis; Cell migration; Cell Movement - genetics; Cytoskeleton; Development and progression; DNA binding proteins; Down-Regulation; Female; Filamins - metabolism; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Kinases; MCF-7 Cells; Medicine and Health Sciences; Metastases; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Morphology; Novels; Proto-Oncogene Proteins c-jun - metabolism; Ribonucleic acid; RNA; Scientific equipment industry; Signal Transduction - genetics; Transcription factors; Tumor cell lines; United States; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224314

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.