Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hallmark of cancer is the paradoxical co-presence, in the same tumour, of local and global DNA hypomethylation together with the regional hypermethylation of certain genes. Due to the oncogenic role of these different DNA methylation alterations, two therapeutic strategies are possible: the use of DNA methylating agents (DMA, such as folate) to inhibit global or local DNA hypomethylation or the use of DNA hypomethylating agents (DHA, such as 5-aza-2-deoxycytidine) to abrogate the accumulation of hypermethylated genes. Here we explored the use of folate to treat gliomas in a mouse model, using tumours induced by either PDGF-B or Ras/Akt overexpression, or by ethylnitrosourea (ENU) treatment. Under all conditions the volume of tumours were significantly less in folate treated mice than in untreated mice. Quantitative methylated DNA immunoprecipitation (qMeDIP) and quantitative methylated specific PCR (qMSP) analysis of methylation status showed that folate treatment, increased the methylation level of DNA repeat elements in tumour and in colorectal tissue and that of MGMT and specific oncogenes (PDGF-B or survivin) in tumours (but not in colorectal tissue), but had no effect on the expression of tumour suppressor genes (p53, PTENorbax) in tumours or in colorectal tissue. This suggests that folate has anti-neoplastic effects in gliomas and that no preneoplastic or neoplastic alterations were observed in unaffected colorectal tissue in response to the potential tumourigenic effects of folate. Collectively, our data support the proposal to include folate as a promising adjuvant in the design of anti-glioma therapeutic protocols in clinical studies.
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PMID:Folate supplementation limits the tumourigenesis in rodent models of gliomagenesis. 2232 70

miRNAs are short non-coding RNAs which function as oncogenes or tumour suppressor gene and regulate gene expression by controlling targets that play role in cancer development and progression. Numerous recent studies have established an association of abnormal expression of miRNA with cervical cancer progression. Although the number of reported deregulated miRNA in cervical cancer is increasing, only a few associations between miRNA and their targets have been studied in cervical cancer. Therefore, we performed a systematic analysis of known dysregulated miRNAs involved in cervical cancer so as to identify critical miRNA targets that could pave way for therapeutic solutions. In this study, miRNAs reported to be dysregulated in cervical cancer were collected and their targets predicted using TargetScan, PicTar and miRanda. These targets were subsequently compared with previously curated gene dataset involved in cervical cancer to derive the putative target dataset. We then compared network properties (composed of degree, betweenness centrality, closeness centrality and clustering coefficient) of the putative, validated and human protein-protein interaction network. Based on the topological properties genes were ranked and observed that the gene targets BIRC5 (survivin), HOXA1 and RARB presenting with high Novoseek score of Genecards were enriched in cervical cancer. BIRC5 is an anti- apoptotic protein while HOXA1 and RARB are transcription factors which play critical role in altering the level of cell cycle and apoptosis associated proteins. Also, miRNA-mRNA network was constructed and it was found that miR-203 and miR-30b could target these genes. The analysis indicates that the genes BIRC5, HOXA1 and RARB are critical targets that play an important regulatory role in cervical cancer pathogenesis.
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PMID:Identification of critical microRNA gene targets in cervical cancer using network properties. 2506 11