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

Xu, Dafeng; Hu, Hao; Ni, Bo; Liu, Xu; Huang, Chen; Zhang, Zizhen; Zhao, Gang

doi:10.1186/s13046-018-0974-1

Cited by 30 publications

(31 citation statements)

References 49 publications

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“…Members of the TMBIM family such as TMBIM1, TMBIM2, TMBIM4, and TMBIM5 are found to be expressed highly in various cancers and also play an important role in cell adhesion and migration [81,82,83,84]. Additionally, TMBIM3 found to be involved in the gastric cancer progression by modulating the glycolytic metabolism [85]. These observations corroborate the high expression of TMBIM6 and its importance in cancer.…”

Section: Discussionmentioning

confidence: 60%

Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

Junjappa

Kim

Park

et al. 2019

Cancers

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Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (−133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer.

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Section: Discussionmentioning

confidence: 60%

Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

Junjappa

Kim

Park

et al. 2019

Cancers

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“…The expression of GRINA is upregulated in breast cancer, colorectal cancer and gastric cancer [13]. A recent article [87] confirmed that GRINA is upregulated in gastric cancer and that its regulation is mediated by c-Myc. The authors found that upon knockdown of GRINA, antiapoptotic Bcl-2 and Bcl-XL were downregulated, while proapoptotic Bax and Bak were upregulated.…”

Section: Transcriptional Regulation Of Grinamentioning

confidence: 99%

Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport

Jiménez-González

Ogalla-García

García-Quintanilla

et al. 2019

IJMS

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The Glutamate Receptor Ionotropic NMDA-Associated Protein 1 (GRINA) belongs to the Lifeguard family and is involved in calcium homeostasis, which governs key processes, such as cell survival or the release of neurotransmitters. GRINA is mainly associated with membranes of the endoplasmic reticulum, Golgi, endosome, and the cell surface, but its presence in the nucleus has not been explained yet. Here we dissect, with the help of different software tools, the potential roles of GRINA in the cell and how they may be altered in diseases, such as schizophrenia or celiac disease. We describe for the first time that the cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export of a subset of genes likely involved in lipid and sterol synthesis, ribosome biogenesis, or cell cycle progression. To support these findings, we include additional evidence based on an exhaustive review of the literature and our preliminary data of the protein–protein interaction network of GRINA.

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“…DEGs are mainly concentrated in angiogenesis, oncostatin-M-mediated signaling pathway, Cytokinecytokine receptor interaction and Glycolysis / Gluconeogenesis. Studies have reported that angiogenesis and glycolysis have a substantial impact on the occurrence and development of gastric cancer [29,30]. In addition, recent studies have found that cytokine-cytokine receptor interactions play an important role in the development of gastric cancer [31].…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Key Biomarkers in Gastric Cancer: Three Genes Jointly Predict Gastric Cancer

Shan

Meng

Guo

et al. 2020

Preprint

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Background: Gastric cancer (GC) is the fifth most common cancer in the world and the second leading cause of cancer death. Gastric cancer screening is one of the effective strategies to reduce the mortality. If we use gastric cancer biomarkers with good clinical effect instead of gastroscopy screening, it can achieve early detection, early diagnosis, early treatment. Methods: We download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which obtained from the Gene Expression Omnibus (GEO) database. The DEGs between gastric cancer and adjacent normal tissues were detect to explore genes that may play a key role in gastric cancer. GO and KEGG analyses of overlap genes were performed by the Metascape online database, the protein-protein interaction (PPI) network was analyzed by the STRING online database, and we obtained the hub genes of PPI network via using the Cytoscape software. The survival curve analysis was performed by km-plotter and the stage plots of hub genes was performed by the GEPIA online database. We selected CDH3, LEF1 and MMP7 as candidate biomarkers to construct a back propagation neural network model. Results: This study shows that MMP7, CDH3 and LEF1 are highly expressed in gastric cancer tissues. Conclusions: The joint prediction of the MMP7, CDH3 and LEF1 is helpful for the early diagnosis of cancer.

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

Cited by 30 publications

References 49 publications

Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport

Screening and Identification of Key Biomarkers in Gastric Cancer: Three Genes Jointly Predict Gastric Cancer

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