GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE117049 Query DataSets for GSE117049
Status Public on Sep 03, 2019
Title The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Expression profiling by array
Summary 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. While 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 adenocarcinomas (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 that 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 6 exons and mainly regulated by NF-ĸB 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 anti-oxidant and/or cisplatin-response networks. We demonstrated that the concomitant knockdown of 4 of these genes, 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.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series
Contributor(s) Rezzonico R, Nottet N, Mari B, Barbry P, Lebrigand K
Citation(s) 31417181
Submission date Jul 12, 2018
Last update date Sep 05, 2019
Contact name Kevin Lebrigand
Organization name IPMC/CNRS
Lab Functional Genomics Platform of Nice-Sophia-Antipolis, France.
Street address 660 route des lucioles
City Valbonne - Sophia-Antipolis
ZIP/Postal code 06560
Country France
Platforms (3)
GPL16558 AB 5500 Genetic Analyzer (Homo sapiens)
GPL17077 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (88)
GSM3265243 LB04-0025L
GSM3265244 LB04-0034L
GSM3265245 LB04-0073L
This SuperSeries is composed of the following SubSeries:
GSE116959 Transcriptome profiling of 57 LUAD samples and 11 peritumoral normal lung tissues
GSE117036 Impact of NLUCAT1 deletion on A549 cells in normoxic and hypoxic conditions
GSE117041 Hypoxic transcriptomic signature of A549 cells (Agilent microarrays)
BioProject PRJNA480904

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE117049_RAW.tar 1.0 Gb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap