The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition.

Simon Grelet, Vanessa Andries, Myriam Polette, Christine Gilles, Katrien Staes, Anne-Pascaline Martin, Claire Kileztky, Christine Terryn, Véronique Dalstein, Chun-Wen Cheng, Chen-Yang Shen, Philippe Birembaut, Frans Van Roy, Béatrice Nawrocki-Raby

Index: J. Pathol. 237 , 25-37, (2015)

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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.Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.