title: miR-200b inhibits prostate cancer EMT, growth and metastasis.
abstract: 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.
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: LaTanya V
authors.initials: LV
authors.lastname: Williams
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Dorina
authors.initials: D
authors.lastname: Veliceasa
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Vinokour
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Volpert
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C410798:AR protein, human; D015820:Cadherins; D005353:Fibronectins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011944:Receptors, Androgen; D014746:Vimentin