title: MicroRNA-194 suppresses prostate cancer migration and invasion by downregulating human nuclear distribution protein.
abstract: Human NudC nuclear distribution protein (hNUDC) is differentially expressed between normal and cancer cells. Based on its marked altered expression and its roles in modulating cell division, cytokineses and migration, a detailed understanding of the mechanisms regulating hNUDC expression in cancer cells is critical. In this study, we identified miR-194 as a downstream target of hNUDC and linked its expression to reduced metastatic capacity and tumorigenicity of prostate cancer (PCa) cells. Using miRNA target prediction programs, hNUDC mRNA was found to contain a potential binding site for miR-194 within its 3'UTR. A Reporter assay confirmed that post-transcriptional regulation of hNUDC was dependent on the miR-194 binding site. Forced expression of miR-194 in PCa cell lines, PC-3 and DU-145, led to a decrease in the mRNA and protein levels of hNUDC. Overexpression of miR-194 in these cells inhibited cell migration and invasion, and induced multinucleated cells. Our data showed that hNUDC knockdown by siRNA significantly reduced the migration and invasion in the PC-3 and DU-145 cells, phenocopying the results of miR-194 overexpression. Furthermore, lentivirus-mediated stable expression of miR-194 in PCa cells reduced the ability of colony formation as detected by a soft agar assay and exhibited significantly less tumorigenic ability in vivo. Our results suggest a novel role for miR-194 in effectively controlling cell metastatic processes in PCa cells via the regulation of hNUDC expression.
authors.affiliation: The Key Laboratory of Gene Engineering of the Chinese Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Kong
authors.affiliation: The Key Laboratory of Gene Engineering of the Chinese Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.
authors.forename: Xu-Shen
authors.initials: XS
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Gene Engineering of the Chinese Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: The Key Laboratory of Gene Engineering of the Chinese Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.
authors.forename: Xiang-You
authors.initials: XY
authors.lastname: Xia
authors.affiliation: The Key Laboratory of Gene Engineering of the Chinese Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; C512648:NUDC protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger