The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress

Leon, Laura Moreno; Gautier, Marine; Allan, Richard; Ilié, Marius; Nottet, Nicolas; Pons, Nicolas; Paquet, Agnès; Lebrigand, Kévin; Truchi, Marin; Fassy, Julien; Magnone, Virginie; Kinnebrew, Garrett; Radovich, Milan; Cheok, Meyling; Barbry, Pascal; Vassaux, Georges; Marquette, Charles Hugo; Ponzio, Gilles; Ivan, Mircea; Pottier, Nicolas; Hofman, Paul; Mari, Bernard; Rezzonico, Roger

doi:10.1038/s41388-019-0935-y

Cited by 82 publications

(55 citation statements)

References 81 publications

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“…Many hypoxia-associated genes have been reported to be correlated to lung adenocarcinoma (Moreno Leon et al, 2019;Cao et al, 2020). Moreover, the use of mRNA gene signatures based on certain tumor microenvironment characteristics showed good prediction potential in lung adenocarcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…For example, overexpression of LBH under hypoxic conditions in gliomas was associated with poor prognosis (Jiang et al, 2019). In lung adenocarcinoma, NLUCAT1, a transcript that is strongly upregulated upon hypoxia, was proved to have significant prognostic value (Moreno Leon et al, 2019). Furthermore, TRB3, which is significantly upregulated by hypoxia, was correlated with a worse prognosis in lung adenocarcinoma patients (Cao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Cao

et al. 2020

Front. Genet.

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Background: A hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma. Methods: Lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index. Results: Four genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4 + T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients. Conclusion: The hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Cao

et al. 2020

Front. Genet.

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“…been previously described for hypoxia lncRNAs, in particular NEAT1, MALAT1, and NLUCAT1 6,11 . A survey of the genomic region surrounding lincNORS using available ChIP-seq data sets (GSE28352) did not reveal functional HIF recruitment sites within the lincNORS proximal regulatory region, in contrast to standard hypoxia responders typically driven by HIF-1 from proximal promoters (e.g., CA9 and miR210/MIR210HG) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Among the best documented is miR-210, the prototypical hypoxia microRNA 4 thought to fine-tune mitochondrial activity to environmental O 2 availability 5 . More recently, the oxygen-sensitive noncoding transcriptome has been expanded to include hypoxia-inducible lncRNAs, such as NEAT1, MALAT1, MEG3, H19, NLUCAT1, HOTAIR, HIF-1-AS2, and MIR210HG [6][7][8][9][10][11] . Although these lncRNAs exert biochemical and phenotypical effects during experimental oxygen deprivation, there is extensive evidence to support their involvement in a broader spectrum of responses 12 .…”

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confidence: 99%

Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

Niculite

Preda³

et al. 2020

Nat Commun

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We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.

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“…We obtained the LUAD-related microarray pro les (GSE116959 [16], GSE21933 [17], GSE31210 [18]) from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). In this study, the datasets that met the following criteria were selected: (a) studies comparing gene expression between human lung adenocarcinoma cancer samples and corresponding normal tissues; (b) the number of samples in each gene expression pro ling dataset shall be more than 30.…”

Section: Data Collection and Preprocessmentioning

confidence: 99%

Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma

Luo

Zheng

Lin

et al. 2020

Preprint

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Background: The role of Serine hydroxymethyltransferase2 (SHMT2) in diverse cancers has attracted increasing attention. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is yet to be studied.Methods: The data of mRNA and clinic in LUAD were respectively downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis and the correlation with immune infiltrates in LUAD.Results: The mRNA expression and protein expression of SHMT2 in LUAD were higher than normal tissue. A Kaplan-Meier analysis showed the lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor for patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD.Conclusions: These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of phenotypes of immune cell infiltration in LUAD.

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The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress

Cited by 82 publications

References 81 publications

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma

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The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress

Cited by 82 publications

References 81 publications

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

Identification of SHMT2&nbsp;as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma

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Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma