Unpublished conference/Abstract (Scientific congresses and symposiums)
Functional characterization of hypoxia-regulated lncRNAs in Non-Small Cell Lung Carcinomas
Gautier, Marine
2019Keystone Symposia : Long Noncoding RNAs: From Molecular Mechanism to Functional Genetics
 

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Keywords :
long non coding RNA; lung cancer; Hypoxia
Abstract :
[en] Hypoxia triggers the activation of several signaling pathways inducing a complex transcriptomic response with multiple consequences on cell survival, migration, invasion and metabolic reprogramming. This regulatory network integrates specific feedbacks and checkpoint signaling loops including epigenetic factors and non-coding RNAs. However, while a large set of miRNAs have been reported as crucial molecular regulators of the hypoxic response, the precise functional characterization of hypoxia-regulated lncRNAs is still in its infancy. Our study aimed at comprehensively characterize the whole set of hypoxia-regulated lncRNAs in lung adenocarcinoma. Using a combination of experimental profiling approaches in both tumor cell lines and patient samples as well as exploring in silico TCGA datasets, we identified a validated signature of lncRNAs correlated to i) the hypoxic status of tumors and ii) the overall survival of patients. Molecular characterization of a subset of these “hypoxa-lcnRNAs” using RNA-Seq, RT-PCR, northern blot and single molecule RNA FISH pointed to 2 interesting candidates with different subcellular localization pattern: i) NLUCAT1, a large nuclear transcript composed of 6 exons and ii) LINC01116, a short cytosolic transcript composed of 3 exons. We next used CRISPR/Cas9-mediated invalidation and transcriptomic analyses as well as RNA-pulldown approaches to functionally characterize their function and mode of action. While NLUCAT1 was mainly identified as a regulator of the NRF2-mediated anti-oxidant response with an impact on cisplatin resistance, LINC01116 was mostly associated to the regulation of cellular morphology, cell-to-cell contact and cell invasion through an alpha catenin gene network. Overall, our study strongly supports the central role of non-coding RNAs in the cellular response to hypoxia and provides the first molecular characterization of 2 hypoxa-lncRNAs contributing to an aggressive phenotype in hypoxic tumors.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Gautier, Marine  ;  Université de Liège - ULiège > GIGA Cancer - Tumours and development biology
Language :
English
Title :
Functional characterization of hypoxia-regulated lncRNAs in Non-Small Cell Lung Carcinomas
Publication date :
2019
Number of pages :
1
Event name :
Keystone Symposia : Long Noncoding RNAs: From Molecular Mechanism to Functional Genetics
Event date :
24-28 Février 2019
Commentary :
Scholarship granted for travel
Available on ORBi :
since 17 May 2021

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