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Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer

Authors: Dan-Hua Xu, Qing Li, Hao Hu, Bo Ni, Xu Liu, Chen Huang, Zi-Zhen Zhang, Gang Zhao

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Recent observations indicate a decreased cancer risk in patients with Alzheimer’s disease (AD). AD is a severe neurodegenerative disorder characterized by progressive cognitive decline. The 8q24 region has been shown to be involved in AD aetiology. We aimed to identify and explore the potential oncogenes or antioncogenes on chromosome 8q24.

Methods

We compared expression of genes on Chromosome 8q24 in 32 pairs of samples from The Cancer Genome Atlas (TCGA) database. We conducted bioinformatics analysis of the commonly used gastric cancer databases and performed clinical verification of gastric cancer samples, combined with assessment of biological function both in vitro and in vivo to determine the relationship between upregulated expression of GRINA and gastric cancer progression. We also explored the molecular mechanism of GRINA upregulation and its function in gastric cancer development and progression.

Results

The expression of GRINA in cancer tissues was significantly higher than that in normal tissues. GRINA indicated poor prognosis in gastric cancer. GRINA promoted the proliferation, migration and invasion capacity of gastric cancer cells. GRINA was transcriptionally mediated by c-Myc and promotes cell cycle transition. GRINA knockdown decreased PI3K/Akt/mTOR signaling and glycolytic metabolism in gastric cancer cells. The apoptosis rate was significantly increased in gastric cancer cell lines after knockdown of GRINA. The expression of pro-apoptotic protein Bax was significantly upregulated, whereas the anti-apoptotic protein Bcl-2 was significantly downregulated in GRINA silenced cells.

Conclusions

Human gastric cancers have increased levels of GRINA, which promotes growth of gastric cancer and inhibits tumor cells apoptosis.
Appendix
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Metadata
Title
Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer
Authors
Dan-Hua Xu
Qing Li
Hao Hu
Bo Ni
Xu Liu
Chen Huang
Zi-Zhen Zhang
Gang Zhao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0974-1

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
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