Titre :

The nuclear hypoxia-regulated nlucat1 long non-coding rna contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress

Auteur(s) :

Moreno Leon, Laura [Auteur]
Université Côte d'Azur [UniCA]
Gautier, Marine [Auteur]
Université Côte d'Azur [UniCA]
Allan, Richard [Auteur]
Université Côte d'Azur [UniCA]
Ilie, Marius [Auteur]
Université Côte d'Azur [UniCA]
Nottet, Nicolas [Auteur]
Université Côte d'Azur [UniCA]
Pons, Nicolas [Auteur]
Université Côte d'Azur [UniCA]
Paquet, Agnes [Auteur]
Université Côte d'Azur [UniCA]
Lebrigand, Kevin [Auteur]
Université Côte d'Azur [UniCA]
Truchi, Marin [Auteur]
Université Côte d'Azur [UniCA]
Fassy, Julien [Auteur]
Université Côte d'Azur [UniCA]
Magnone, Virginie [Auteur]
Université Côte d'Azur [UniCA]
Kinnebrew, Garrett [Auteur]
Indiana University School of Medicine
Radovich, Milan [Auteur]
Indiana University School of Medicine
Cheok, Meyling Hua-Chen [Auteur]
Institut pour la recherche sur le cancer de Lille [Lille] [IRCL]
barbry, pascal [Auteur]
Université Côte d'Azur [UniCA]
Vassaux, Georges [Auteur]
Université Côte d'Azur [UniCA]
Marquette, Charles-Hugo [Auteur]
Université Côte d'Azur [UniCA]
Ponzio, Gilles [Auteur]
Université Côte d'Azur [UniCA]
Ivan, Mircea [Auteur]
Indiana University School of Medicine
Pottier, Nicolas [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - EA 4483
Hofman, Paul [Auteur]
Université Côte d'Azur [UniCA]
Mari, Bernard [Auteur]
Université Côte d'Azur [UniCA]
Rezzonico, Roger [Auteur]
FHU OncoAge - Pathologies liées à l’âge [CHU Nice] [OncoAge]

Titre de la revue :

Oncogene

Nom court de la revue :

Oncogene

Numéro :

38

Pagination :

7146–7165

Date de publication :

2019-08-15

ISSN :

1476-5594

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance ...
Lire la suite >Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regulation and function following hypoxic stress are still largely unexplored. Combining profiling studies on early-stage lung adenocarcinoma (LUAD) biopsies and on A549 LUAD cell lines cultured in normoxic or hypoxic conditions, we identified a subset of lncRNAs that are both correlated with the hypoxic status of tumors and regulated by hypoxia in vitro. We focused on a new transcript, NLUCAT1, which is strongly upregulated by hypoxia in vitro and correlated with hypoxic markers and poor prognosis in LUADs. Full molecular characterization showed that NLUCAT1 is a large nuclear transcript composed of six exons and mainly regulated by NF-κB and NRF2 transcription factors. CRISPR-Cas9-mediated invalidation of NLUCAT1 revealed a decrease in proliferative and invasive properties, an increase in oxidative stress and a higher sensitivity to cisplatin-induced apoptosis. Transcriptome analysis of NLUCAT1-deficient cells showed repressed genes within the antioxidant and/or cisplatin-response networks. We demonstrated that the concomitant knockdown of four of these genes products, GPX2, GLRX, ALDH3A1, and PDK4, significantly increased ROS-dependent caspase activation, thus partially mimicking the consequences of NLUCAT1 inactivation in LUAD cells. Overall, we demonstrate that NLUCAT1 contributes to an aggressive phenotype in early-stage hypoxic tumors, suggesting it may represent a new potential therapeutic target in LUADs.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CNRS
Université de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
• Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290

Date de dépôt :

2022-02-02T10:23:23Z
2024-02-15T10:27:17Z