Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer
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 explor...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0974-1 |
| _version_ | 1828384342835986432 |
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| author | Dan-Hua Xu Qing Li Hao Hu Bo Ni Xu Liu Chen Huang Zi-Zhen Zhang Gang Zhao |
| author_facet | Dan-Hua Xu Qing Li Hao Hu Bo Ni Xu Liu Chen Huang Zi-Zhen Zhang Gang Zhao |
| author_sort | Dan-Hua Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:02:23Z |
| format | Article |
| id | doaj.art-da961a8c8e9348f6a783fe7aa55bce2e |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-10T05:02:23Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-da961a8c8e9348f6a783fe7aa55bce2e2022-12-22T02:01:22ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-12-0137111810.1186/s13046-018-0974-1Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancerDan-Hua Xu0Qing Li1Hao Hu2Bo Ni3Xu Liu4Chen Huang5Zi-Zhen Zhang6Gang Zhao7Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0974-1Chromosome 8q24C-MycProliferationApoptosisGlycolysis |
| spellingShingle | Dan-Hua Xu Qing Li Hao Hu Bo Ni Xu Liu Chen Huang Zi-Zhen Zhang Gang Zhao Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer Journal of Experimental & Clinical Cancer Research Chromosome 8q24 C-Myc Proliferation Apoptosis Glycolysis |
| title | Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| title_full | Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| title_fullStr | Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| title_full_unstemmed | Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| title_short | Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| title_sort | transmembrane protein grina modulates aerobic glycolysis and promotes tumor progression in gastric cancer |
| topic | Chromosome 8q24 C-Myc Proliferation Apoptosis Glycolysis |
| url | http://link.springer.com/article/10.1186/s13046-018-0974-1 |
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