OBJECTIVES: To investigate the functional roles of microRNA-205 in the modulation of novel cancer pathways in prostate cancer cells. METHODS: Functional studies of microRNA-205 were carried out to investigate cell proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145) by restoration of mature microRNA. In silico database and genome-wide gene expression analyses were carried out to identify molecular targets and pathways mediated by microRNA-205. Loss-of-function studies were applied to microRNA-205 target genes. RESULTS: Restoration of microRNA-205 in cancer cell lines significantly inhibited cancer cell migration and invasion. Our data showed that the centromere protein F gene was overexpressed in prostate cancer clinical specimens and was a direct target of microRNA-205 regulation. Silencing of centromere protein F significantly inhibited cancer cell migration and invasion. Furthermore, MCM7, an oncogenic gene functioning downstream of centromere protein F, was identified by si-centromere protein F transfectants in prostate cancer cells. CONCLUSIONS: Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.
OBJECTIVES: To investigate the functional roles of microRNA-205 in the modulation of novel cancer pathways in prostate cancer cells. METHODS: Functional studies of microRNA-205 were carried out to investigate cell proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145) by restoration of mature microRNA. In silico database and genome-wide gene expression analyses were carried out to identify molecular targets and pathways mediated by microRNA-205. Loss-of-function studies were applied to microRNA-205 target genes. RESULTS: Restoration of microRNA-205 in cancer cell lines significantly inhibited cancer cell migration and invasion. Our data showed that the centromere protein F gene was overexpressed in prostate cancer clinical specimens and was a direct target of microRNA-205 regulation. Silencing of centromere protein F significantly inhibited cancer cell migration and invasion. Furthermore, MCM7, an oncogenic gene functioning downstream of centromere protein F, was identified by si-centromere protein F transfectants in prostate cancer cells. CONCLUSIONS: Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.
Authors: Elise R Pfaltzgraff; Gretchen M Roth; Paul M Miller; Anneelizabeth G Gintzig; Ryoma Ohi; David M Bader Journal: Mol Biol Cell Date: 2016-05-04 Impact factor: 4.138