Cleavage of SNAP‐25 ameliorates cancer pain in a mouse model of melanoma

Olbrich, Katrin; Costard, Lara S.; Möser, Christine V.; Syhr, Katharina M.J.; King-Himmelreich, Tanya S.; Wolters, Miriam; Schmidtko, Achim; Geißlinger, Gerd; Niederberger, Ellen

doi:10.1002/ejp.904

Cited by 7 publications

(4 citation statements)

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“…It was reported that SNAP25 was overexpressed in colon cancer samples, and abnormal expression of SNAP25 indicated a poor prognosis of colon cancer patients ( 21 ). Contradictorily, SNAP25 was identified to inhibit cancer progression as cleavage of SNAP25 could ameliorate cancer pain of a mouse melanoma model and a comprehensive bioinformatic analysis of GBM indicated that SNAP25 might act as a GBM suppressor and a biomarker in GBM treatment ( 28 , 29 ). Furthermore, SNAP25 was found to have significantly lower expression levels in medulloblastoma and SNAP25 was crucial for dendrite formation which is associated with the effects of targeted chemotherapy ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis

et al. 2021

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BackgroundNeuronal activity regulated by synaptic communication exerts an important role in tumorigenesis and progression in brain tumors. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function ‘vesicle’ about synaptic connectivity were identified, and synaptosomal-associated protein 25 (SNAP25), one of those proteins, was found to have discrepant expression levels in neuropathies. However, the specific mechanism and prognostic value of SNAP25 during glioma progression remain unclear.MethodsUsing RNA sequencing data from The Cancer Genome Atlas (TCGA) database, the differential synaptosis-related genes between low grade glioma (LGG) and glioblastoma (GBM) were identified as highly correlated. Cox proportional hazards regression analysis and survival analysis were used to differentiate the outcome of low- and high-risk patients, and the Chinese Glioma Genome Atlas (CGGA) cohort was used for validation of the data set. RT-qPCR, western blot, and immunohistochemistry assays were performed to examine the expression level of SNAP25 in glioma cells and samples. Functional assays were performed to identify the effects of SNAP25 knockdown and overexpression on cell viability, migration, and invasion. Liquid chromatography-high resolution mass spectrometry (LC-MS)-based metabolomics approach was presented for identifying crucial metabolic disturbances in glioma cells. In situ mouse xenograft model was used to investigate the role of SNAP25 in vivo. Then, an immunofluorescence assay of the xenograft tissue was applied to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2).ResultsSNAP25 was decreased in level of expression in glioma tissues and cell lines, and low-level SNAP25 indicated an unfavorable prognosis of glioma patients. SNAP25 inhibited cell proliferation, migration, invasion and fostered glutamine metabolism of glioma cells, exerting a tumor suppressor role. Overexpressed SNAP25 exerted a lower expression level of MAP2, indicating poor neuronal plasticity and connectivity. SNAP25 could regulate glutaminase (GLS)-mediated glutaminolysis, and GLS knockdown could rescue the anti-tumor effect of SNAP25 in glioma cells. Moreover, upregulated SNAP25 also decreased tumor volume and prolonged the overall survival (OS) of the xenograft mouse.ConclusionSNAP25, a tumor suppressor inhibited carcinogenesis of glioma via limiting glutamate metabolism by regulating GLS expression, as well as inhibiting dendritic formation, which could be considered as a novel molecular therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 99%

SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis

et al. 2021

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“…SNAP25 may serve as a biomarker for glioblastoma inhibitors and glioblastoma therapy. [19,20] Since SNAP25 basically plays a key role in regulating synaptic activity of alveolar metastasis between adjacent cells in the nervous system, [19,20] SNAP25 may play a role in activation of glioma cell interactions, thereby affecting the growth of brain cancer. SNAP25 has also been shown to be a potential prognostic biomarker for prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Role of SNAP25 on the occurrence and development of eosinophilic gastritis

et al. 2023

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Eosinophilic gastritis is characterized by gastrointestinal symptoms accompanied by peripheral eosinophilia. This study aims to explore the association between eosinophilic gastritis and Synaptosome Associated Protein 25 (SNAP25), and provide a new direction for the diagnosis and treatment of eosinophilic gastritis. GSE54043 was downloaded from the gene expression omnibus database. Differentially expressed genes (DEGs) were screened. The functions of common DEGs were annotated by Database for Annotation, Visualization and Integrated Discovery and Metascape. The protein–protein interaction network of common DEGs was obtained by Search Tool for the Retrieval of Interacting Genes and visualized by Cytoscape. Significant modules were identified from the protein–protein interaction network. A total of 186 patients with eosinophilic gastritis were recruited. The clinical data were recorded and the expression levels of CPE, SST, PCSK2, SNAP25, and SYT4 were detected. Pearson chi-square test and Spearman correlation coefficient were used to analyze the relationship between eosinophilic gastritis and related parameters. Univariate and multivariate Logistic regression were used for further analysis. 353 DEGs were presented. The top 10 genes screened by cytoHubb were shown, and Veen diagram figured out 5 mutual genes. Pearson’s chi-square test showed that SNAP25 (P < .001) was significantly associated with eosinophilic gastritis. Spearman correlation coefficient showed a significant correlation between eosinophilic gastritis and SNAP25 (ρ = −0.569, P < .001). Univariate logistic regression analysis showed that SNAP25 (OR = 0.046, 95% CI: 0.018–0.116, P < .001) was significantly associated with eosinophilic gastritis. Multivariate logistic regression analysis showed that SNAP25 (OR = 0.024, 95% CI: 0.007–0.075, P < .001) was significantly associated with eosinophilic gastritis. The low expression of SNAP25 gene in eosinophilic gastritis is associated with a higher risk of eosinophilic gastritis.

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“…During the advanced stages of cancer, synaptosomal, associated protein of 25 kDa (SNAP-25), a membrane-binding protein in neurons, is thought to promote tumor development through autophagy, and to play a role in the process of tumor pain (32,33). Furthermore, studies have shown that the expression of SNAP-25 alters the characteristics of synaptic transmission, leading to pathological changes in neuronal circuits in psychiatric diseases (34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑744‑5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

et al. 2021

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Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for ~57% of all gliomas and 48% of all malignant primary central nervous system tumors in the United States. Abnormal expression of the replication factor C subunit 2 (RFC2) gene and microRNA (miR)-744-5p is associated with tumorigenic characteristics, including cellular proliferation, migration and invasiveness. However, the mechanism underlying the interaction between miR-744-5p and RFC2 in GBM remains unknown. Reverse transcription-quantitative (RT-q) PCR analysis of RFC2 and miR-744-5p was performed using GBM tumor tissues and cells, and the association between miR-744-5p and RFC2 was determined by dual-luciferase reporter assay. Cell Counting Kit 8, 5-bromo-2-deoxyuridine (BrdU), wound-healing and cellular adhesion assays, as well as the detection of caspase-3 activity and western blotting were used to detect cellular proliferation, migration and adhesion, caspase-3 activity, and Bax and Bcl-2 protein expression, respectively, in GBM cells. The results of the present study demonstrated that RFC2 expression was increased in GBM tissues and cell lines. Overexpression of RFC2 promoted cellular proliferation, migration, adhesion and an increase in Bcl-2 protein levels, and suppressed cellular caspase-3 activity and Bax protein expression, while silencing RFC2 resulted in the opposite effect. The effects of miR-744-5p inhibition were similar to those of RFC2 overexpression. Moreover, miR-744-5p was found to target RFC2 in GBM cells, and inhibiting the expression of RFC2 suppressed GBM tumorigenesis. In conclusion, the present study demonstrated that miR-744-5p targets RFC2 and suppresses the progression of GBM by repressing cellular proliferation, migration and Bcl-2 protein expression, and effectively promoting caspase-3 activity and Bax protein expression. These findings suggest a new target for the clinical treatment and improved prognosis of patients with GBM in the future.

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Cleavage of SNAP‐25 ameliorates cancer pain in a mouse model of melanoma

Cited by 7 publications

References 35 publications

SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis

SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis

Role of SNAP25 on the occurrence and development of eosinophilic gastritis

MicroRNA‑744‑5p inhibits glioblastoma malignancy by suppressing replication factor C subunit 2

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