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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 mollevi
Last modified by llecam
Group name EquipeLLC
Item Type Journal Article
Title AMPK/HuR-Driven IL-20 Post-Transcriptional Regulation in Psoriatic Skin
Creator Garcin et al.
Author G. Garcin
Author I. Guiraud
Author M. Lacroix
Author C. Genthon
Author S. Rialle
Author J. M. Joujoux
Author L. Meunier
Author T. Lavabre-Bertrand
Author P. E. Stoebner
Author L. Le Gallic
Abstract IL-20 is involved in the development of skin psoriasis. The molecular mechanisms underlying IL-20 overexpression in psoriatic epidermis remain to be elucidated. We showed that IL-20 was primarily upregulated in psoriatic skin at the post-transcriptional level. The RNA-binding protein HuR relocalized to the cytoplasm of keratinocytes (KCs) of psoriatic patients, suggesting that it stabilizes numerous transcripts, as observed in the human KC cell lines used to assess IL-20 mRNA. We characterized epidermal HuR RNA targets in psoriatic skin using ribonucleoprotein immunoprecipitation analyzed via high-throughput sequencing. Numerous transcripts that are upregulated in psoriasis were targeted by HuR, supporting the participation of HuR in pathogenic processes such as morphological changes, innate and adaptive immune responses, and metabolic inflammatory responses. Finally, we identified the metabolic sensor AMP-activated protein kinase (AMPK) as being responsible for HuR cytoplasmic relocalization because its activity was severely impaired in human psoriatic epidermis, and in vivo drug-mediated AMPK inhibition in mouse epidermis promoted HuR cytoplasmic localization, IL-20 overproduction, acanthosis, and hyperkeratosis. These results provide insights into the molecular links between metabolism and post-transcriptional networks during chronic inflammation.Journal of Investigative Dermatology advance online publication, 6 August 2015; doi:10.1038/jid.2015.282.
Publication J Invest Dermatol
Date Jun 15 2015
Journal Abbr The Journal of investigative dermatology
DOI 10.1038/jid.2015.282
ISSN 1523-1747 (Electronic) 0022-202X (Linking)
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Date Added 2018/11/14 - 11:59:48
Date Modified 2022/08/30 - 12:34:05
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