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

The ARHI (aplasia Ras homologue member I, also known as DIRAS3) gene shows 60.0% sequence homology to the Ras proto-oncogene and was the first mater-nally-imprinted tumor suppressor gene identified in the Ras family. It is constitutively expressed from the paternal allele in normal breast, ovary, heart, liver, pancreas, thyroid and brain tissues, and is lost or markedly down-regulated primarily in breast, ovarian, pancreas and thyroid tumor tissues. We have investigated the expression, LOH (loss of heterozygosity) and methylation status of this gene in glial tumors and peripheral blood samples of 21 patients, and in seven normal brain tissue samples. Gene expression by real time reverse transcriptase polymerase chain reaction (RT-PCR) was found to be increased in 14 and decreased in seven of the 21 tumors. The LOH was detected by fragment analysis, using five labeled polymorphic markers specific for the 1p31 region, in two of the tumors. Methylation status of the CpG island I, II and III was evaluated using COBRA (combined bisulfite restriction analysis) and RFLP (restriction fragment length polymorphism) in 21 tumors and also a hypermethylated healthy volunteer as a positive control, revealed that only two tumors had hypermethylation in CpG island I (of which one also had LOH). These results suggest that LOH and hypermethylation may be one mechanism of silencing the ARHI gene expression and development of glial tumor development.
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PMID:Aplasia ras homologous member I gene and development of glial tumors. 2405 1

This study was conducted to evaluate the role of tumor suppressor gene ras homologue member I (ARHI) in human glioma tumors. We examined expression of ARHI in human glioma tumors and normal brain tissue and also in 4 different glioma cell lines. Furthermore, the effects of ARHI over-expression produced by cellular transfection on the growth of human glioma U251 cells cultured in vitro were also studied. Expression of ARHI was evaluated in samples of glioma tumors obtained from 59 patients who underwent surgery at the Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China. Ten samples of normal brain tissue were used as controls. Additionally, in vitro studies were conducted in which a recombinant vector carrying ARHI cDNA was constructed and transfected into U251 glioma cells with reduced expression of ARHI. Following transfection, the MTT assay, flow cytometry, TUNEL procedure, Transwell assay, and wound-healing test were employed to evaluate the biological functions of ARHI in U251 glioma cells in vitro. Analyses of mRNA and protein expression revealed that ARHI was significantly down-regulated in glioma tissues as well as in 4 malignant glioma cell lines. Over-expression of ARHI resulted in suppression of glioma cell proliferation, arrest of cell cycle progression, reduction in cell migration and invasion, and promotion of cell apoptosis. Collectively, our data highlight the importance of ARHI in glioma progression and provide the first biological basis for ARHI as a novel candidate target for gene therapy of glioma.
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PMID:Over-expression of ARHI decreases tumor growth, migration, and invasion in human glioma. 2445 8

Hypermethylation can downregulate many tumor suppressor gene expressions. Aplasia Ras homologue member I (ARHI, DIRAS3) is one of the maternally imprinted tumor suppressors in the RAS superfamily. This chapter overviewed the importance of ARHI methylation and expression phenomes in various types of cancers, although the exact mechanisms remain unclear. As an imprinted gene, aberrant DNA methylation of the paternal allele of ARHI was identified as a primary inhibitor of ARHI expression. The role of methylation in the CpG islands of the ARHI promoter region vary among ovarian cancers, breast cancers, hepatocellular carcinoma, colon cancers, pancreatic cancer osteosarcoma, glial tumors, follicular thyroid carcinoma, or lung cancers. The methylation of ARHI provides a new insight to understand molecular mechanisms of tumorigenesis and progression of cancers.
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PMID:The Role of Methylation in the CpG Island of the ARHI Promoter Region in Cancers. 3294 95