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   the impact of dna demethylation on the upregulation of the nrn1 and tnfaip3 genes associated with advanced gastric cancer  
   
نویسنده wisnieski fernanda ,santos leonardo caires ,calcagno danielle queiroz ,geraldis jaqueline cruz ,gigek carolina oliveira ,anauate ana carolina ,chen elizabeth suchi ,rasmussen lucas trevizani ,payão spencer luiz marques ,artigiani ricardo ,demachki samia ,assumpção paulo pimentel ,lourenço laercio gomes ,arasaki carlos haruo ,pabinger stephan ,krainer julie ,leal mariana ferreira ,burbano rommel rodriguez ,smith marilia arruda cardoso
منبع journal of molecular medicine - 2020 - دوره : 98 - شماره : 5 - صفحه:707 -717
چکیده    Gastric cancer (gc) is the third leading cause of cancer-related death worldwide. very few therapeutic options are currently available in this neoplasia. the use of 5-aza-2′-deoxycytidine (5-azadc) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. epigenetic manipulation of gc cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. therefore, we compared the gene expression profile of 5-azadc-treated and untreated gc cell lines by a microarray assay. among the genes identified in this analysis, we selected nrn1 and tnfaip3 to be evaluated for gene expression by rt-qpcr and dna methylation by bisulfite dna next-generation sequencing in 43 and 52 pairs of gc and adjacent non-neoplastic tissue samples, respectively. we identified 83 candidate genes modulated by dna methylation in gc cell lines. increased expression of nrn1 and tnfaip3 was associated with advanced tumours (p < 0.05). we showed that increased nrn1 and tnfaip3 expression seems to be regulated by dna demethylation in gc samples: inverse correlations between the mrna and dna methylation levels in the promoter of nrn1 (p < 0.05) and the intron of tnfaip3 (p < 0.05) were detected. reduced nrn1 promoter methylation was associated with iii/iv tnm stage tumours (p = 0.03) and the presence of helicobacter pylori infection (p = 0.02). the identification of demethylated activated genes in gc be useful in clinical practice, stratifying patients who are less likely to benefit from 5-azadc-based therapies.
کلیدواژه cancer therapy ,dna methylation ,5-aza-2′-deoxycytidine ,nrn1 ,tnfaip3
آدرس universidade federal de são paulo, departamento de morfologia e genética, departamento de medicina, brazil, universidade federal de são paulo, departamento de morfologia e genética, brazil, universidade federal do pará, programa de pós-graduação em oncologia e ciências médicas, brazil, universidade federal de são paulo, departamento de morfologia e genética, brazil, universidade federal de são paulo, departamento de patologia, brazil, universidade federal de são paulo, departamento de morfologia e genética, brazil, universidade federal de são paulo, departamento de morfologia e genética, brazil, hemocentro da faculdade de medicina de marília, brazil, hemocentro da faculdade de medicina de marília, brazil, universidade federal de são paulo, departamento de patologia, brazil, universidade federal do pará, programa de pós-graduação em oncologia e ciências médicas, brazil, universidade federal do pará, programa de pós-graduação em oncologia e ciências médicas, brazil, universidade federal de são paulo, departamento de cirurgia, brazil, universidade federal de são paulo, departamento de cirurgia, brazil, center for health & bioresources, austrian institute of technology, austria, center for health & bioresources, austrian institute of technology, austria, universidade federal de são paulo, departamento de morfologia e genética, brazil. universidade federal do pará, programa de pós-graduação em oncologia e ciências médicas, brazil, universidade federal do pará, programa de pós-graduação em oncologia e ciências médicas, brazil. hospital ophir loyola, laboratório de biologia molecular, brazil, universidade federal de são paulo, departamento de morfologia e genética, brazil
 
     
   
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