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http://purl.uniprot.org/citations/32285140http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32285140http://www.w3.org/2000/01/rdf-schema#comment"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 may be useful in clinical practice, stratifying patients who are less likely to benefit from 5-AZAdC-based therapies. KEY MESSAGES: Higher expression of NRN1 and TNFAIP3 is associated with advanced gastric cancer (GC). NRN1 promoter hypomethylation contributes to gene upregulation in advanced GC. TNFAIP3 intronic-specific CpG site demethylation contributes to gene upregulation in GC. These findings may be useful to stratify GC patients who are less likely to benefit from DNA demethylating-based therapies."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.org/dc/terms/identifier"doi:10.1007/s00109-020-01902-1"xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Pabinger S."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Chen E.S."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Santos L.C."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Demachki S."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Burbano R.R."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Rasmussen L.T."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Assumpcao P.P."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Calcagno D.Q."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Leal M.F."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Gigek C.O."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Arruda Cardoso Smith M."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Artigiani R."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Lourenco L.G."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Wisnieski F."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Payao S.L.M."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Anauate A.C."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Arasaki C.H."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Geraldis J.C."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/author"Krainer J."xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/name"J Mol Med (Berl)"xsd:string
http://purl.uniprot.org/citations/32285140http://purl.uniprot.org/core/pages"707-717"xsd:string