title: miR-25 Modulates Invasiveness and Dissemination of Human Prostate Cancer Cells via Regulation of αv- and α6-Integrin Expression.
abstract: Altered microRNA (miRNA; miR) expression is associated with tumor formation and progression of various solid cancers. A major challenge in miRNA expression profiling of bulk tumors is represented by the heterogeneity of the subpopulations of cells that constitute the organ, as well as the tumor tissue. Here, we analyzed the expression of miRNAs in a subpopulation of epithelial stem/progenitor-like cells in human prostate cancer [prostate cancer stem cell (PCSC)] and compared their expression profile to more differentiated cancer cells. In both cell lines and clinical prostate cancer specimens, we identified that miR-25 expression in PCSCs was low/absent and steadily increased during their differentiation into cells with a luminal epithelial phenotype. Functional studies revealed that overexpression of miR-25 in prostate cancer cell lines and selected subpopulation of highly metastatic and tumorigenic cells (ALDH(high)) strongly affected the invasive cytoskeleton, causing reduced migration in vitro and metastasis via attenuation of extravasation in vivo. Here, we show, for the first time, that miR-25 can act as a tumor suppressor in highly metastatic PCSCs by direct functional interaction with the 3'-untranslated regions of proinvasive αv- and α6-integrins. Taken together, our observations suggest that miR-25 is a key regulator of invasiveness in human prostate cancer through its direct interactions with αv- and α6-integrin expression.
authors: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors: E
authors: E
authors: Zoni
authors: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors: G
authors: G
authors: van der Horst
authors: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors: A F
authors: AF
authors: van de Merbel
authors: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, the Netherlands.
authors: L
authors: L
authors: Chen
authors: Department of Biology, YCR Cancer Research Unit, University of York, York, North Yorkshire, United Kingdom.
authors: J K
authors: JK
authors: Rane
authors: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors: R C M
authors: RC
authors: Pelger
authors: Department of Biology, YCR Cancer Research Unit, University of York, York, North Yorkshire, United Kingdom.
authors: A T
authors: AT
authors: Collins
authors: Institute of Biosciences and Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors: T
authors: T
authors: Visakorpi
authors: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, the Netherlands.
authors: B E
authors: BE
authors: Snaar-Jagalska
authors: Department of Biology, YCR Cancer Research Unit, University of York, York, North Yorkshire, United Kingdom.
authors: N J
authors: NJ
authors: Maitland
authors: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands. G.van_der_Pluijm@lumc.nl.
authors: G
authors: G
authors: van der Pluijm
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D039503:Integrin alpha6 / Q000096:biosynthesis* / Q000235:genetics; D039564:Integrin alphaV / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D039503:Integrin alpha6; D039564:Integrin alphaV; C543351:MIRN25 microRNA, human; D035683:MicroRNAs