Dataset Information

Upregulated expression of LncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 is correlated with unfavorable clinical outcomes in cancers.

ABSTRACT:

Background

The nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a long non-coding RNA aberrantly expressed in human malignancies. We aimed to analyze available data to evaluate the correlation between NNT-AS1 expression and cancer prognosis.

Methods

Literature retrieval was performed by systematic searching related databases from inception to April 2, 2020. Studies regarding correlation between NNT-AS1 expression, survival outcomes and clinical characteristics of cancer patients were collected and pooled to calculate the the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs).

Results

Ten studies comprising 699 patients were included, all of which were conducted in China according to literature selection criteria. Overexpression of NNT-AS1 had a significant association with unfavorable overall survival (OS) (HR = 2.08, 95% CI: 1.84-2.36, P < 0.001). Stratified analysis showed that tumor type, sample size, follow-up months, and survival analysis approach did not change the predictive value of NNT-AS1 on OS. Furthermore, elevated NNT-AS1 level had significant association with distant metastasis (DM) (OR = 2.45, 95% CI: 1.39-4.30), lymph node metastasis (LNM) (OR = 3.92, 95% CI: 1.35-11.41), TNM stage (OR = 4.25, 95% CI: 1.71-10.56), and vascular invasion (OR = 3.98, 95% CI: 2.06-7.71), but was not associated with age and gender. The TCGA dataset further consistently showed that the NNT-AS1 expression was associated with poor OS and disease-free survival.

Conclusions

High expression of NNT-AS1 is associated with unfavorable survival outcomes and poor clinicopathologic characteristics. However, large-cohort data and geographical studies are still needed to further validate the prognostic value of NNT-AS1 in cancers.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7489002 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Upregulated expression of LncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 is correlated with unfavorable clinical outcomes in cancers.

Zhang Chenghao C Ren Xiaolei X Liu Zhongyue Z Tu Chao C

BMC cancer 20200914 1

<h4>Background</h4>The nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a long non-coding RNA aberrantly expressed in human malignancies. We aimed to analyze available data to evaluate the correlation between NNT-AS1 expression and cancer prognosis.<h4>Methods</h4>Literature retrieval was performed by systematic searching related databases from inception to April 2, 2020. Studies regarding correlation between NNT-AS1 expression, survival outcomes and clinical characteristics ...[more]

PMID: 32928135

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Project description:Endothelial dysfunction is a critical, initiating step in the development of hypertension (HTN) and mitochondrial reactive oxygen species (ROS) are important contributors to endothelial dysfunction. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the nicotinamide nucleotide transhydrogenase (Nnt) gene that are associated with endothelial dysfunction and increased risk for HTN. NNT is emerging as an important enzyme that regulates mitochondrial NADPH levels and mitochondrial redox balance by supporting the thiol dependent peroxidase systems in the mitochondria. We have previously shown that the absence of NNT in C57Bl/6J animals promotes a more severe hypertensive phenotype through reductions in •NO and endothelial dependent vessel dilation. However, the impact of NNT on human endothelial cell function remains unclear. We utilized NNT directed shRNA in human aortic endothelial cells to test the hypothesis that NNT critically regulates mitochondrial redox balance and endothelial function in response to angiotensin II (Ang II). We demonstrate that NNT expression and activity are elevated in response to the mitochondrial dysfunction and oxidative stress associated with Ang II treatment. Knockdown of NNT led to a significant elevation of mitochondrial ROS production and impaired glutathione peroxidase and glutathione reductase activities associated with a reduction in the NADPH/NADP+ ratio. Loss of NNT also promoted mitochondrial dysfunction, disruption of the mitochondrial membrane potential, and impaired ATP production in response to Ang II. Finally, we observed that, while the loss of NNT augmented eNOS phosphorylation at Ser1177, neither eNOS activity nor nitric oxide production were similarly increased. The results from these studies clearly demonstrate that NNT is critical for the maintenance of mitochondrial redox balance and mitochondrial function. Loss of NNT and disruption of redox balance leads to oxidative stress that compromises eNOS activity that could have a profound effect on the endothelium dependent regulation of vascular tone.

Dataset Information

Upregulated expression of LncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 is correlated with unfavorable clinical outcomes in cancers.

Background

Methods

Results

Conclusions

Publications

Upregulated expression of LncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 is correlated with unfavorable clinical outcomes in cancers.

Similar Datasets

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