Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10-8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.
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PMID:Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus. 2717 99

This study explored the regulatory role of microRNA-1271 (miR-1271) in glioblastoma multiforme (GBM) proliferation and invasion via calcium/calmodulin-dependent protein kinase 2 (CaMKK2). MiR-1271 and CaMKK2 expression were quantified in normal human astrocyte cells, GBM cell lines, and low- and high-grade glioma tissues. MKI67 expression in GBM cells was measured using quantitative real-time polymerase chain reaction. The target relationship between miR-1271 and the CAMKK2 gene was confirmed using the luciferase reporter assay. MTT and Transwell assays were used to analyze the role of miR-1271 and CAMKK2 in cell proliferation and invasion. Finally, CaMKK2 expression and AKT phosphorylation were detected by western blotting. MiR-1271 was significantly downregulated in high-grade glioma tissues and GBM cell lines. Conversely, CAMKK2 mRNA expression was upregulated in high-grade glioma tissues and GBM cell lines. We observed that miR-1271 directly targeted the 3'-untranslated region of CAMKK2, indicating an inverse relationship with miR-1271. Overexpressing miR-1271 inhibited GBM cell proliferation and invasion, whereas inhibiting miR-1271 increased cell proliferation and invasion. Silencing CAMKK2 expression also inhibited GBM cell proliferation and invasion. Furthermore, overexpressing miR-1271 inhibited AKT phosphorylation and MKI67 mRNA expression by targeting CAMKK2. These results indicate that miR-1271 regulates GBM cell proliferation and invasion, and that these effects involve directly targeting the CAMKK2 gene. Therefore, miR-1271 may serve as a new therapeutic target for developing GBM treatments.
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PMID:MiR-1271 regulates glioblastoma cell proliferation and invasion by directly targeting the CAMKK2 gene. 3279 Oct 96