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COX-2 induces oncogenic micro RNA miR655 in human breast cancer
Scientific Reports
  • Mousumi Majumder, Department of Biology, Brandon University
  • Leanna Dunn, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario
  • Ling Liu, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario
  • Asma Hasan, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario
  • Krista Vincent, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario & Department of Oncology, University of Alberta
  • Muriel Brackstone, Department of Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario & Lawson Research Institute
  • David Hess, Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario & Robarts Research Institute
  • Peeyush K Lala, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario & Department of Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario
Document Type
Article
Publication Date
1-10-2018
URL with Digital Object Identifier
https://doi.org/10.1038/s41598-017-18612-3
Abstract

We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA miR655 in human breast cancer cells by activation of EP4. MiR655 expression positively correlated with COX-2 in genetically disparate breast cancer cell lines and increased in all cell lines when grown as spheroids, implicating its link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid formation and Epithelial to Masenchymal transition (EMT). Conversely, knocking down miR655 in aggressive MCF7-COX2 and SKBR3-COX2 cells reverted these phenotypes. MCF7-miR655 cells displayed upregulated NOTCH/ WNT genes; both pathway inhibitors abrogated miR655-induced spheroid formation, linking miR655 with SLC-related pathways. MiR655 expression was dependent on EP4 activity and EP4 downstream signaling pathways PI3K/AKT, ERK and NF-kB and led to TGF beta resistance for Smad3 phosphorylation. Tail vein injection of MCF7-miR655 and SKBR3-miR655 cells in NOD/SCID/GUSB-null mice revealed increased lung colony growth and micrometastases to liver and spleen. MiR655 expression was significantly high in human breast tumors (n = 105) compared to non-tumor tissues (n = 20) and associated with reduced patient survival. Thus miR655 could serve as a prognostic breast cancer biomarker.

Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Mousumi Majumder, Leanna Dunn, Ling Liu, Asma Hasan, et al.. "COX-2 induces oncogenic micro RNA miR655 in human breast cancer" Scientific Reports Vol. 8 Iss. 1 (2018) p. 327
Available at: http://works.bepress.com/david_hess/1/