PubMed:26411452 JSONTXT

{"project":"LitCoin-sentences","denotations":[{"id":"T4","span":{"begin":382,"end":680},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":166},"obj":"Sentence"},{"id":"T2","span":{"begin":167,"end":310},"obj":"Sentence"},{"id":"T3","span":{"begin":311,"end":381},"obj":"Sentence"},{"id":"T5","span":{"begin":681,"end":769},"obj":"Sentence"},{"id":"T6","span":{"begin":770,"end":976},"obj":"Sentence"},{"id":"T7","span":{"begin":977,"end":1071},"obj":"Sentence"},{"id":"T8","span":{"begin":1072,"end":1238},"obj":"Sentence"},{"id":"T9","span":{"begin":1239,"end":1368},"obj":"Sentence"},{"id":"T10","span":{"begin":1369,"end":1530},"obj":"Sentence"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-entities","denotations":[{"id":"10816","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10817","span":{"begin":40,"end":57},"obj":"GeneOrGeneProduct"},{"id":"10818","span":{"begin":78,"end":90},"obj":"GeneOrGeneProduct"},{"id":"10819","span":{"begin":135,"end":152},"obj":"GeneOrGeneProduct"},{"id":"10820","span":{"begin":288,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10821","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10822","span":{"begin":484,"end":491},"obj":"GeneOrGeneProduct"},{"id":"10823","span":{"begin":492,"end":495},"obj":"GeneOrGeneProduct"},{"id":"10824","span":{"begin":524,"end":529},"obj":"CellLine"},{"id":"10825","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10826","span":{"begin":640,"end":657},"obj":"GeneOrGeneProduct"},{"id":"10827","span":{"begin":673,"end":675},"obj":"GeneOrGeneProduct"},{"id":"10828","span":{"begin":763,"end":765},"obj":"GeneOrGeneProduct"},{"id":"10829","span":{"begin":780,"end":790},"obj":"SequenceVariant"},{"id":"10830","span":{"begin":791,"end":794},"obj":"SequenceVariant"},{"id":"10831","span":{"begin":815,"end":827},"obj":"GeneOrGeneProduct"},{"id":"10832","span":{"begin":834,"end":838},"obj":"GeneOrGeneProduct"},{"id":"10833","span":{"begin":878,"end":880},"obj":"GeneOrGeneProduct"},{"id":"10834","span":{"begin":947,"end":955},"obj":"ChemicalEntity"},{"id":"10835","span":{"begin":977,"end":980},"obj":"SequenceVariant"},{"id":"10836","span":{"begin":1037,"end":1039},"obj":"GeneOrGeneProduct"},{"id":"10837","span":{"begin":1048,"end":1050},"obj":"GeneOrGeneProduct"},{"id":"10838","span":{"begin":1090,"end":1094},"obj":"GeneOrGeneProduct"},{"id":"10839","span":{"begin":1106,"end":1121},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10840","span":{"begin":1227,"end":1229},"obj":"GeneOrGeneProduct"},{"id":"10841","span":{"begin":1246,"end":1258},"obj":"GeneOrGeneProduct"},{"id":"10842","span":{"begin":1287,"end":1295},"obj":"OrganismTaxon"},{"id":"10843","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10844","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10845","span":{"begin":1413,"end":1415},"obj":"GeneOrGeneProduct"},{"id":"10846","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"},{"id":"10847","span":{"begin":1488,"end":1496},"obj":"ChemicalEntity"},{"id":"10848","span":{"begin":1525,"end":1529},"obj":"GeneOrGeneProduct"}],"attributes":[{"id":"A10","pred":"db_id","subj":"10825","obj":"MESH:D011471"},{"id":"A13","pred":"db_id","subj":"10828","obj":"NCBIGene:367"},{"id":"A2","pred":"db_id","subj":"10817","obj":"NCBIGene:367"},{"id":"A11","pred":"db_id","subj":"10826","obj":"NCBIGene:367"},{"id":"A25","pred":"db_id","subj":"10840","obj":"NCBIGene:367"},{"id":"A31","pred":"db_id","subj":"10846","obj":"MESH:D011471"},{"id":"A24","pred":"db_id","subj":"10839","obj":"MESH:D011471"},{"id":"A27","pred":"db_id","subj":"10842","obj":"NCBITaxon:9606"},{"id":"A4","pred":"db_id","subj":"10819","obj":"NCBIGene:367"},{"id":"A32","pred":"db_id","subj":"10847","obj":"MESH:D000728"},{"id":"A18","pred":"db_id","subj":"10833","obj":"NCBIGene:367"},{"id":"A21","pred":"db_id","subj":"10836","obj":"NCBIGene:367"},{"id":"A30","pred":"db_id","subj":"10845","obj":"NCBIGene:367"},{"id":"A5","pred":"db_id","subj":"10820","obj":"MESH:D011471"},{"id":"A28","pred":"db_id","subj":"10843","obj":"MESH:D011471"},{"id":"A12","pred":"db_id","subj":"10827","obj":"NCBIGene:367"},{"id":"A26","pred":"db_id","subj":"10841","obj":"NCBIGene:79083"},{"id":"A9","pred":"db_id","subj":"10824","obj":"NCBITaxon:9606"},{"id":"A29","pred":"db_id","subj":"10844","obj":"MESH:D009369"},{"id":"A1","pred":"db_id","subj":"10816","obj":"MESH:D011471"},{"id":"A8","pred":"db_id","subj":"10823","obj":"NCBIGene:2078"},{"id":"A3","pred":"db_id","subj":"10818","obj":"NCBIGene:79083"},{"id":"A16","pred":"db_id","subj":"10831","obj":"NCBIGene:79083"},{"id":"A22","pred":"db_id","subj":"10837","obj":"NCBIGene:367"},{"id":"A14","pred":"db_id","subj":"10829","obj":"DBSNP:rs11891426"},{"id":"A15","pred":"db_id","subj":"10830","obj":"DBSNP:rs11891426"},{"id":"A6","pred":"db_id","subj":"10821","obj":"MESH:D011471"},{"id":"A33","pred":"db_id","subj":"10848","obj":"NCBIGene:79083"},{"id":"A7","pred":"db_id","subj":"10822","obj":"NCBIGene:7113"},{"id":"A17","pred":"db_id","subj":"10832","obj":"NCBIGene:79083"},{"id":"A20","pred":"db_id","subj":"10835","obj":"DBSNP:rs11891426"},{"id":"A23","pred":"db_id","subj":"10838","obj":"NCBIGene:79083"},{"id":"A19","pred":"db_id","subj":"10834","obj":"MESH:D000728"}],"namespaces":[{"prefix":"_base","uri":"https://w3id.org/biolink/vocab/"},{"prefix":"MESH","uri":"http://id.nlm.nih.gov/mesh/"},{"prefix":"NCBITaxon","uri":"https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id="},{"prefix":"NCBIGene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"OMIM","uri":"https://www.omim.org/entry/"},{"prefix":"DBSNP","uri":"https://www.ncbi.nlm.nih.gov/snp/"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin_Mondo","denotations":[{"id":"T1","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":288,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":297,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":584,"end":606},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1106,"end":1114},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1268,"end":1276},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0008315"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0008315"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0004992"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0042489"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0005280"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0005280"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-SeqVar","denotations":[{"id":"T1","span":{"begin":780,"end":790},"obj":"SequenceVariant"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-GeneOrGeneProduct-v2","denotations":[{"id":"T1","span":{"begin":0,"end":8},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":40,"end":57},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":58,"end":65},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":78,"end":90},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":135,"end":152},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":274,"end":303},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":305,"end":308},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":373,"end":380},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":484,"end":491},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":492,"end":500},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":550,"end":553},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":640,"end":657},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":658,"end":665},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":815,"end":827},"obj":"GeneOrGeneProduct"},{"id":"T15","span":{"begin":834,"end":838},"obj":"GeneOrGeneProduct"},{"id":"T16","span":{"begin":853,"end":858},"obj":"GeneOrGeneProduct"},{"id":"T17","span":{"begin":859,"end":867},"obj":"GeneOrGeneProduct"},{"id":"T18","span":{"begin":881,"end":888},"obj":"GeneOrGeneProduct"},{"id":"T19","span":{"begin":990,"end":1000},"obj":"GeneOrGeneProduct"},{"id":"T20","span":{"begin":1005,"end":1020},"obj":"GeneOrGeneProduct"},{"id":"T21","span":{"begin":1090,"end":1094},"obj":"GeneOrGeneProduct"},{"id":"T22","span":{"begin":1230,"end":1237},"obj":"GeneOrGeneProduct"},{"id":"T23","span":{"begin":1246,"end":1258},"obj":"GeneOrGeneProduct"},{"id":"T24","span":{"begin":1313,"end":1316},"obj":"GeneOrGeneProduct"},{"id":"T25","span":{"begin":1400,"end":1404},"obj":"GeneOrGeneProduct"},{"id":"T26","span":{"begin":1433,"end":1441},"obj":"GeneOrGeneProduct"},{"id":"T27","span":{"begin":1442,"end":1445},"obj":"GeneOrGeneProduct"},{"id":"T28","span":{"begin":1525,"end":1529},"obj":"GeneOrGeneProduct"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-GeneOrGeneProduct-v0","denotations":[{"id":"T1","span":{"begin":0,"end":8},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":40,"end":57},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":58,"end":65},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":78,"end":90},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":135,"end":152},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":274,"end":303},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":305,"end":308},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":365,"end":372},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":373,"end":380},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":484,"end":491},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":492,"end":500},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":530,"end":535},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":550,"end":553},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":640,"end":657},"obj":"GeneOrGeneProduct"},{"id":"T15","span":{"begin":658,"end":665},"obj":"GeneOrGeneProduct"},{"id":"T16","span":{"begin":725,"end":731},"obj":"GeneOrGeneProduct"},{"id":"T17","span":{"begin":815,"end":827},"obj":"GeneOrGeneProduct"},{"id":"T18","span":{"begin":834,"end":838},"obj":"GeneOrGeneProduct"},{"id":"T19","span":{"begin":853,"end":858},"obj":"GeneOrGeneProduct"},{"id":"T20","span":{"begin":859,"end":867},"obj":"GeneOrGeneProduct"},{"id":"T21","span":{"begin":881,"end":888},"obj":"GeneOrGeneProduct"},{"id":"T22","span":{"begin":990,"end":1000},"obj":"GeneOrGeneProduct"},{"id":"T23","span":{"begin":1005,"end":1020},"obj":"GeneOrGeneProduct"},{"id":"T24","span":{"begin":1021,"end":1029},"obj":"GeneOrGeneProduct"},{"id":"T25","span":{"begin":1090,"end":1094},"obj":"GeneOrGeneProduct"},{"id":"T26","span":{"begin":1115,"end":1121},"obj":"GeneOrGeneProduct"},{"id":"T27","span":{"begin":1230,"end":1237},"obj":"GeneOrGeneProduct"},{"id":"T28","span":{"begin":1246,"end":1258},"obj":"GeneOrGeneProduct"},{"id":"T29","span":{"begin":1313,"end":1316},"obj":"GeneOrGeneProduct"},{"id":"T30","span":{"begin":1330,"end":1336},"obj":"GeneOrGeneProduct"},{"id":"T31","span":{"begin":1337,"end":1340},"obj":"GeneOrGeneProduct"},{"id":"T32","span":{"begin":1343,"end":1348},"obj":"GeneOrGeneProduct"},{"id":"T33","span":{"begin":1400,"end":1404},"obj":"GeneOrGeneProduct"},{"id":"T34","span":{"begin":1413,"end":1421},"obj":"GeneOrGeneProduct"},{"id":"T35","span":{"begin":1433,"end":1441},"obj":"GeneOrGeneProduct"},{"id":"T36","span":{"begin":1442,"end":1445},"obj":"GeneOrGeneProduct"},{"id":"T37","span":{"begin":1497,"end":1507},"obj":"GeneOrGeneProduct"},{"id":"T38","span":{"begin":1525,"end":1529},"obj":"GeneOrGeneProduct"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-Disease-MeSH","denotations":[{"id":"T1","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":274,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":584,"end":606},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":640,"end":648},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":947,"end":955},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1115,"end":1121},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":1488,"end":1496},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A5","pred":"originalLabel","subj":"T5","obj":"D004198"},{"id":"A10","pred":"originalLabel","subj":"T10","obj":"D009369"},{"id":"A11","pred":"originalLabel","subj":"T11","obj":"C566426"},{"id":"A2","pred":"originalLabel","subj":"T2","obj":"C566426"},{"id":"A8","pred":"originalLabel","subj":"T8","obj":"D009369"},{"id":"A4","pred":"originalLabel","subj":"T4","obj":"C566426"},{"id":"A3","pred":"originalLabel","subj":"T3","obj":"C566426"},{"id":"A7","pred":"originalLabel","subj":"T7","obj":"D014770"},{"id":"A1","pred":"originalLabel","subj":"T1","obj":"D011471"},{"id":"A12","pred":"originalLabel","subj":"T12","obj":"D014770"},{"id":"A9","pred":"originalLabel","subj":"T9","obj":"C566426"},{"id":"A6","pred":"originalLabel","subj":"T6","obj":"D014770"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-GeneOrGeneProduct-v3","denotations":[{"id":"T1","span":{"begin":40,"end":57},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":78,"end":90},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":135,"end":152},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":484,"end":491},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":492,"end":500},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":640,"end":657},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":815,"end":827},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":834,"end":838},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":1005,"end":1029},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":1090,"end":1094},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":1246,"end":1258},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":1525,"end":1529},"obj":"GeneOrGeneProduct"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin_Mondo_095","denotations":[{"id":"T1","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":288,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0008315"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0008315"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0008315"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0008315"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0008315"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0005070"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0008315"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-MeSH-Disease-2","denotations":[{"id":"T1","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":274,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":584,"end":606},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1115,"end":1121},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"ID:","subj":"T1","obj":"D011471"},{"id":"A2","pred":"ID:","subj":"T2","obj":"C566426"},{"id":"A3","pred":"ID:","subj":"T3","obj":"C566426"},{"id":"A4","pred":"ID:","subj":"T4","obj":"C566426"},{"id":"A5","pred":"ID:","subj":"T5","obj":"D004198"},{"id":"A6","pred":"ID:","subj":"T6","obj":"DISEASE"},{"id":"A7","pred":"ID:","subj":"T6","obj":"D009369"},{"id":"A8","pred":"ID:","subj":"T8","obj":"C566426"},{"id":"A9","pred":"ID:","subj":"T9","obj":"D009369"},{"id":"A10","pred":"ID:","subj":"T10","obj":"C566426"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin_CellLine","denotations":[{"id":"T1","span":{"begin":524,"end":529},"obj":"CellLine"}],"attributes":[{"id":"A1","pred":"cellosaurus_accession_id","subj":"T1","obj":"CVCL_2025"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-MONDO_bioort2019","denotations":[{"id":"T1","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":274,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":584,"end":606},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1115,"end":1121},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"D011471"},{"id":"A2","pred":"#label","subj":"T2","obj":"C566426"},{"id":"A3","pred":"#label","subj":"T3","obj":"C566426"},{"id":"A4","pred":"#label","subj":"T4","obj":"C566426"},{"id":"A5","pred":"#label","subj":"T5","obj":"D004198"},{"id":"A6","pred":"#label","subj":"T6","obj":"D009369"},{"id":"A7","pred":"#label","subj":"T7","obj":"C566426"},{"id":"A8","pred":"#label","subj":"T8","obj":"D009369"},{"id":"A9","pred":"#label","subj":"T9","obj":"C566426"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-Chemical-MeSH-CHEBI","denotations":[{"id":"T1","span":{"begin":40,"end":48},"obj":"ChemicalEntity"},{"id":"T2","span":{"begin":135,"end":143},"obj":"ChemicalEntity"},{"id":"T3","span":{"begin":640,"end":648},"obj":"ChemicalEntity"},{"id":"T4","span":{"begin":947,"end":955},"obj":"ChemicalEntity"},{"id":"T5","span":{"begin":1488,"end":1496},"obj":"ChemicalEntity"}],"attributes":[{"id":"A1","pred":"ID:","subj":"T1","obj":"ChemicalEntity"},{"id":"A2","pred":"ID:","subj":"T2","obj":"ChemicalEntity"},{"id":"A3","pred":"ID:","subj":"T3","obj":"ChemicalEntity"},{"id":"A4","pred":"ID:","subj":"T4","obj":"ChemicalEntity"},{"id":"A5","pred":"ID:","subj":"T5","obj":"ChemicalEntity"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-NCBITaxon-2","denotations":[{"id":"T1","span":{"begin":1287,"end":1295},"obj":"OrganismTaxon"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"LitCoin-training-merged","denotations":[{"id":"T1","span":{"begin":524,"end":529},"obj":"CellLine"},{"id":"T5","span":{"begin":1488,"end":1496},"obj":"ChemicalEntity"},{"id":"T4","span":{"begin":947,"end":955},"obj":"ChemicalEntity"},{"id":"T3","span":{"begin":640,"end":648},"obj":"ChemicalEntity"},{"id":"T2","span":{"begin":135,"end":143},"obj":"ChemicalEntity"},{"id":"T35811","span":{"begin":40,"end":48},"obj":"ChemicalEntity"},{"id":"T12","span":{"begin":1525,"end":1529},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":1246,"end":1258},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":1090,"end":1094},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":1005,"end":1029},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":834,"end":838},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":815,"end":827},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":640,"end":657},"obj":"GeneOrGeneProduct"},{"id":"T68614","span":{"begin":492,"end":500},"obj":"GeneOrGeneProduct"},{"id":"T32017","span":{"begin":484,"end":491},"obj":"GeneOrGeneProduct"},{"id":"T24929","span":{"begin":135,"end":152},"obj":"GeneOrGeneProduct"},{"id":"T51022","span":{"begin":78,"end":90},"obj":"GeneOrGeneProduct"},{"id":"T71376","span":{"begin":40,"end":57},"obj":"GeneOrGeneProduct"},{"id":"T44355","span":{"begin":1442,"end":1445},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T38643","span":{"begin":1343,"end":1348},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T27829","span":{"begin":1313,"end":1316},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T84965","span":{"begin":1115,"end":1121},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T17675","span":{"begin":584,"end":606},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T77784","span":{"begin":550,"end":553},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T23506","span":{"begin":305,"end":308},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T87555","span":{"begin":274,"end":303},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T36849","span":{"begin":9,"end":24},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T69263","span":{"begin":1287,"end":1295},"obj":"OrganismTaxon"},{"id":"T72192","span":{"begin":780,"end":790},"obj":"SequenceVariant"}],"attributes":[{"id":"A7","pred":"#label","subj":"T27829","obj":"C566426"},{"id":"A8","pred":"#label","subj":"T38643","obj":"D009369"},{"id":"A6","pred":"#label","subj":"T84965","obj":"D009369"},{"id":"A1","pred":"cellosaurus_accession_id","subj":"T1","obj":"CVCL_2025"},{"id":"A2","pred":"ID:","subj":"T2","obj":"ChemicalEntity"},{"id":"A4","pred":"ID:","subj":"T4","obj":"ChemicalEntity"},{"id":"A3","pred":"ID:","subj":"T3","obj":"ChemicalEntity"},{"id":"A9","pred":"#label","subj":"T44355","obj":"C566426"},{"id":"A32026","pred":"#label","subj":"T17675","obj":"D004198"},{"id":"A65287","pred":"#label","subj":"T23506","obj":"C566426"},{"id":"A56662","pred":"#label","subj":"T36849","obj":"D011471"},{"id":"A37297","pred":"#label","subj":"T87555","obj":"C566426"},{"id":"A11463","pred":"#label","subj":"T77784","obj":"C566426"},{"id":"A45875","pred":"ID:","subj":"T35811","obj":"ChemicalEntity"},{"id":"A5","pred":"ID:","subj":"T5","obj":"ChemicalEntity"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"26411452-3#102#109#gene7113","span":{"begin":484,"end":491},"obj":"gene7113"},{"id":"26411452-3#110#113#gene2078","span":{"begin":492,"end":495},"obj":"gene2078"},{"id":"26411452-3#258#275#gene367","span":{"begin":640,"end":657},"obj":"gene367"},{"id":"26411452-3#168#171#diseaseC0376358","span":{"begin":550,"end":553},"obj":"diseaseC0376358"},{"id":"26411452-3#168#171#diseaseC0600139","span":{"begin":550,"end":553},"obj":"diseaseC0600139"},{"id":"26411452-3#168#171#diseaseC0376358","span":{"begin":550,"end":553},"obj":"diseaseC0376358"},{"id":"26411452-3#168#171#diseaseC0600139","span":{"begin":550,"end":553},"obj":"diseaseC0600139"},{"id":"26411452-3#168#171#diseaseC0376358","span":{"begin":550,"end":553},"obj":"diseaseC0376358"},{"id":"26411452-3#168#171#diseaseC0600139","span":{"begin":550,"end":553},"obj":"diseaseC0600139"},{"id":"26411452-8#7#19#gene79083","span":{"begin":1246,"end":1258},"obj":"gene79083"},{"id":"26411452-8#74#77#diseaseC0376358","span":{"begin":1313,"end":1316},"obj":"diseaseC0376358"},{"id":"26411452-8#74#77#diseaseC0600139","span":{"begin":1313,"end":1316},"obj":"diseaseC0600139"}],"relations":[{"id":"102#109#gene7113168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"102#109#gene7113168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"102#109#gene7113168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"102#109#gene7113168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"102#109#gene7113168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"102#109#gene7113168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#102#109#gene7113","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"110#113#gene2078168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"110#113#gene2078168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"110#113#gene2078168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"110#113#gene2078168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"110#113#gene2078168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"110#113#gene2078168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#110#113#gene2078","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"258#275#gene367168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"258#275#gene367168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"258#275#gene367168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"258#275#gene367168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"258#275#gene367168#171#diseaseC0376358","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0376358"},{"id":"258#275#gene367168#171#diseaseC0600139","pred":"associated_with","subj":"26411452-3#258#275#gene367","obj":"26411452-3#168#171#diseaseC0600139"},{"id":"7#19#gene7908374#77#diseaseC0376358","pred":"associated_with","subj":"26411452-8#7#19#gene79083","obj":"26411452-8#74#77#diseaseC0376358"},{"id":"7#19#gene7908374#77#diseaseC0600139","pred":"associated_with","subj":"26411452-8#7#19#gene79083","obj":"26411452-8#74#77#diseaseC0600139"}],"text":"Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.\nGenome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T\u003eG in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH."}