miR-200b inhibits prostate cancer EMT, growth and metastasis

• Published in: PloS one Vol. 8; no. 12; p. e83991
• Main Authors: Williams, LaTanya V, Veliceasa, Dorina, Vinokour, Elena, Volpert, Olga V
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2013; Public Library of Science (PLoS)
• Subjects: Androgen receptors; Androgens; Angiogenesis; Animals; Apoptosis; B cells; Biological activity; Biology; Blotting, Western; Cadherins - genetics; Cadherins - metabolism; Cancer; Cancer metastasis; Cell Cycle; Cell Movement; Cell Proliferation; Development and progression; DNA methylation; E-cadherin; Epithelial-Mesenchymal Transition; Epithelium; Fibronectin; Fibronectins; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Humans; Immunoenzyme Techniques; Laboratory animals; Male; Markers; Medicine; Mesenchyme; Metastases; Metastasis; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Neoplasm Invasiveness; Neoplasm Metastasis; Penicillin; Post-transcription; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - secondary; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA, Messenger - genetics; Stem cells; Transcription (Genetics); Tumor Cells, Cultured; Tumorigenesis; Tumorigenicity; Tumors; Urology; Vimentin; Vimentin - genetics; Vimentin - metabolism; Xenograft Model Antitumor Assays; United States > US; Illinois; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083991

miRNA regulate gene expression at post-transcriptional level and fine-tune the key biological processes, including cancer progression. Here, we demonstrate the involvement of miR-200 b in the metastatic spread of prostate cancer. We identified miR-200 b as a downstream target of androgen receptor and linked its expression to decreased tumorigenicity and metastatic capacity of the prostate cancer cells. Overexpression of miR-200 b in PC-3 cells significantly inhibited their proliferation and the formation of subcutaneous tumors. Moreover, in an orthotopic model, miR-200 b blocked spontaneous metastasis and angiogenesis by PC-3 cells. This decreased metastatic potential was likely due to the reversal of the epithelial-to-mesenchymal transition, as was evidenced by increased pan-epithelial marker E-cadherin and specific markers of prostate epithelium, cytokeratins 8 and 18. In contrast, mesenchymal markers, fibronectin and vimentin, were significantly downregulated by miR-200 b. Our results suggest an important role for miR-200 b in prostate cancer progression and indicate its potential utility for prostate cancer therapy.