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

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

Edité par CCSD ; Wiley -

International audience. In this study, we explore the role of the human NANOS3 germline gene in lung tumour progression. We report that Nanos3 is overexpressed by invasive lung cancer cells and represents a new prognostic marker for non-small cell lung carcinomas (NSCLC). We also show that Nanos3 gene expression is restricted in testis and brain and is regulated by epigenetic events. Moreover, we demonstrate that Nanos3 is upregulated in cultured cells undergoing epithelialmesenchymal transition (EMT). Nanos3 overexpression in human NSCLC cell lines enhances their invasiveness by upregulating EMT, whereas its silencing induces mesenchymalepithelial transition. Nanos3 represses E-cadherin at the transcriptional level and upregulates Vimentin post-transcriptionally. Also, we show that Nanos3 binds mRNAs encoding Vimentin and regulates the length of the 3' poly(A) tail of VIM mRNA Finally, Nanos3 can also protect Vimentin mRNA from microRNA-mediated repression. We thus demonstrate a new role for Nanos3 in the acquisition of invasiveness by human lung tumour cells and propose a new mechanism of post-transcriptional regulation of EMT.

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