title: The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition.
abstract: We have explored the role of the human NANOS3 gene in lung tumour progression. We show that NANOS3 is over-expressed by invasive lung cancer cells and is a prognostic marker for non-small cell lung carcinomas (NSCLCs). NANOS3 gene expression is restricted in testis and brain and is regulated by epigenetic events. It is up-regulated in cultured cells undergoing epithelial - mesenchymal transition (EMT). NANOS3 over-expression in human NSCLC cell lines enhances their invasiveness by up-regulating EMT, whereas its silencing induces mesenchymal - epithelial transition. NANOS3 represses E-cadherin at the transcriptional level and up-regulates vimentin post-transcriptionally. Also, we show that NANOS3 binds mRNAs encoding vimentin and regulates the length of their poly(A) tail. Finally, NANOS3 can also protect vimentin mRNA from microRNA-mediated repression. We thus demonstrate a role for NANOS3 in the acquisition of invasiveness by human lung tumour cells and propose a new mechanism of post-transcriptional regulation of EMT.
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Grelet
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Belgium.|Molecular Cell Biology Unit, Inflammation Research Centre, Ghent, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andries
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.|Laboratory of Histology, CHU Reims, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.affiliation: Laboratory of Developmental and Tumour Biology, GIGA-Cancer, University of Liège, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Gilles
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Belgium.|Molecular Cell Biology Unit, Inflammation Research Centre, Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Staes
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.
authors.forename: Anne-Pascaline
authors.initials: AP
authors.lastname: Martin
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Kileztky
authors.affiliation: Plateforme Imagerie Cellulaire et Tissulaire, University of Reims Champagne-Ardenne, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Terryn
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.|Laboratory of Histology, CHU Reims, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalstein
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.|Laboratory of Histology, CHU Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Belgium.|Molecular Cell Biology Unit, Inflammation Research Centre, Ghent, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Van Roy
authors.affiliation: INSERM UMR-S 903, SFR CAP-Santé, University of Reims Champagne-Ardenne, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nawrocki-Raby
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D035683:MicroRNAs; C524848:NANOS3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014746:Vimentin
keywords: NANOS3; epithelial-mesenchymal transition; lung cancer; post-transcriptional regulation; tumour invasion