Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai, Harcharan K.; Martin, Andrew; King, Andrew; Appadu, Usha D.; Jones, Huw; Selway, Richard; Gullan, Richard; Pilkington, Geoffrey J.

doi:10.3892/ijo.2016.3739

Cited by 18 publications

(17 citation statements)

References 39 publications

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“…We also identi ed the EGFR pathway as driving miR-9-1 overexpression in malignant meningioma, via FOS, which is predicted to bind to the promoter/enhancer region of miR-9-1 (43). This is in keeping with previous studies, which have shown that EGF/ERBB2 receptors and FOS are upregulated, and are involved in the molecular process that drives meningioma pathogenesis and/or progression to highergrade tumors (32,(44)(45)(46)(47)(48). FOS knock out experiments supported this observation, resulting in decreased miR-9-1 and increased E-cadherin in malignant KT21-MG1 cells (49,50).…”

Section: Discussionsupporting

confidence: 92%

miR-9-1 Is a New Circulating Biomarker for Higher-grade Meningioma Regulated via the EGFR-FOS Network

Daniele¹,

Negroni²,

Ferluga³

et al. 2020

Preprint

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Background: Meningiomas are the most common primary CNS tumors. According to the World Health Organization Classification (WHO), they are classified as benign (grade I), atypical (grade II), and anaplastic/malignant (grade III). Chemotherapy has proven ineffective in treating these tumors, which are primarily managed by surgery, radiotherapy, or a combination of them. Morbidity and mortality correlate with meningioma grade. Currently, risk assessment for treatment is based on the radiological assessment of tumor size, tumor growth rate, and/or clinical progression of symptoms. Methods: We performed a cancer miRNA array in an in vitro model of meningioma in order to identify circulating biomarkers in meningioma patients. We validated the miRNA biomarker candidate in cells and tissues and analyzed its regulation. We then investigated expression in tissues and blood. Results: We identified miR-9-1 as significantly overexpressed in atypical and anaplastic cells compared to benign. We further demonstrated that miR-9-1 overexpression is due to increased levels of FOS via upregulation of the EGFR receptor, and showed that miR-9-1 and FOS are upregulated in a cohort of higher-grade meningioma biopsies. Next, we isolated circulating exosomes from meningioma patients’ serum samples, and found higher levels of miR-9-1 in higher-grade compared to low-grade meningiomas patients. Conclusions: Overall, our study shows overexpression and the mechanism of miR-9-1 regulation and suggests miR-9-1 as a novel circulating biomarker candidate to identify tumor grade in meningioma.

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Section: Discussionsupporting

confidence: 92%

miR-9-1 Is a New Circulating Biomarker for Higher-grade Meningioma Regulated via the EGFR-FOS Network

Daniele¹,

Negroni²,

Ferluga³

et al. 2020

Preprint

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“…In addition, GO analysis revealed that the enriched ontological categories among the DEGs mainly included ECM organization, cell adhesion, angiogenesis, signal transduction and negative regulation of cell proliferation. Previous studies have revealed that matrix metalloproteinases (MMPs), which are mediators of invasion and angiogenesis, may serve important roles in the invasion and recurrence of meningioma ( 28 , 29 ). Indeed, cumulative evidence has demonstrated that the contribution of MMPs to tumor progression may be associated with the regulation of cell adhesion, the control of apoptosis via the release of factors associated with cell death or survival, and the proteolysis of the ECM ( 28 , 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have revealed that matrix metalloproteinases (MMPs), which are mediators of invasion and angiogenesis, may serve important roles in the invasion and recurrence of meningioma ( 28 , 29 ). Indeed, cumulative evidence has demonstrated that the contribution of MMPs to tumor progression may be associated with the regulation of cell adhesion, the control of apoptosis via the release of factors associated with cell death or survival, and the proteolysis of the ECM ( 28 , 30 , 31 ). Previous studies have demonstrated that the aforementioned GO terms are potentially important events in meningioma development and tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and pathways in meningioma by bioinformatics analysis

Dai

Chu

et al. 2018

Oncol Lett

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Meningioma is the most frequently occurring type of brain tumor. The present study aimed to conduct a comprehensive bioinformatics analysis of key genes and relevant pathways involved in meningioma, and acquire further insight into the underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) in 47 meningioma samples as compared with 4 normal meninges were identified. Subsequently, these DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, a protein-protein interaction (PPI) network of the identified DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes and visualized using Cytoscape. In total, 1,683 DEGs were identified, including 66 upregulated and 1,617 downregulated genes. The GO analysis results revealed that the DEGs were significantly associated with the ‘protein binding’, ‘cytoplasm’, ‘extracellular matrix (ECM) organization’ and ‘cell adhesion’ terms. The KEGG analysis results demonstrated the significant pathways included ‘AGE-RAGE signaling pathway in diabetic complications’, ‘PI3K-Akt signaling pathway’, ‘ECM-receptor interaction’ and ‘cell adhesion molecules’. The top five hub genes obtained from the PPI network were JUN, PIK3R1, FOS, AGT and MYC, and the most enriched KEGG pathways associated with the four obtained modules were ‘chemokine signaling pathway’, ‘cytokine-cytokine receptor interaction’, ‘allograft rejection’, and ‘complement and coagulation cascades’. In conclusion, bioinformatics analysis identified a number of potential biomarkers and relevant pathways that may represent key mechanisms involved in the development and progression of meningioma. However, these findings require verification in future experimental studies.

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“…Meningiomas may invade tissue using a wide array of proteases, including matrix metalloproteinases (MMPs) and ADAMs (a disintegrin and metalloproteinase), which may be seen even in histologically benign meningiomas. 14 One study also found that up to 20% of atypical meningiomas show hypermethylation of tissue inhibitor of metalloproteinase 3 (TIMP3), encoding a protein involved in cell motility and invasion through the regulation of metalloproteinase function, which appears to be associated with aggressive behavior. 15,16 Disruption of the leptomeninges from brain invasion, surgery, and/or radiation may facilitate access of chemotactic factors and/or growth factors from tumor cells to the melanocytes residing in the leptomeninges and stimulate cell migration.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma

Harati

Magaki

et al. 2017

Neuropathology

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Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported. We add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases.

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Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Cited by 18 publications

References 39 publications

miR-9-1 Is a New Circulating Biomarker for Higher-grade Meningioma Regulated via the EGFR-FOS Network

miR-9-1 Is a New Circulating Biomarker for Higher-grade Meningioma Regulated via the EGFR-FOS Network

Identification of key genes and pathways in meningioma by bioinformatics analysis

Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma

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