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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Added by Nathalie Bonnefoy
Group name EquipeNB
Item Type Journal Article
Title Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating immune cells
Creator Groeneveld et al.
Author Svenja Groeneveld
Author Julien Faget
Author Nadine Zangger
Author Etienne Meylan
Abstract The epithelial-mesenchymal transition-inducing transcription factor Snail contributes to tumor progression in different malignancies. In the present study, we used a transcriptomics approach to elucidate the mechanism of Snail-mediated tumor growth promotion in a KrasLSL-G12D/+;p53fl/fl mouse model of lung adenocarcinoma. We discovered that Snail mediated the downregulation of the imprinted Dlk1-Dio3 locus, a complex genomic region containing protein-coding genes and non-coding RNAs that has been linked to tumor malignancy in lung cancer patients. The Dlk1-Dio3 locus repression mediated by Snail was found to occur specifically in several populations of tumor-infiltrating immune cells. It could be reproduced in primary splenocytes upon ex vivo culture with conditioned medium from Snail-expressing cancer cell lines, which suggests that a Snail-induced soluble factor secreted by the cancer cells mediates the Dlk1-Dio3 locus repression in immune cells, particularly in lymphocytes. Our findings furthermore point towards the contribution of Snail to an inflammatory tumor microenvironment, which is in line with our previous report of the Snail-mediated recruitment of pro-tumorigenic neutrophils to the lung tumors. This underlines an important role for Snail in influencing the immune compartment of lung tumors and thus contributing to disease progression.
Publication Oncotarget
Volume 9
Issue 64
Pages 32331-32345
Date Aug 17, 2018
Journal Abbr Oncotarget
Language eng
DOI 10.18632/oncotarget.25965
ISSN 1949-2553
Library Catalog PubMed
Extra PMID: 30190790 PMCID: PMC6122344
Tags Dlk1-Dio3 locus, lung adenocarcinoma, microenvironment, miRNA, original, Snail
Date Added 2019/05/28 - 18:47:43
Date Modified 2019/05/28 - 22:16:45
Notes and Attachments PubMed entry (Attachment)
Texte intégral (Attachment)


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