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Functional Epigenetic Analysis of Prostate Carcinoma: A Role for Seryl-tRNA Synthetase?

机译:前列腺癌的功能性表观遗传学分析:Seryl-tRNA合成酶的作用?

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Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to reexpress transcriptional silenced genes may identify such inactivated genes for needing further evaluation. We aimed to identify genes so far not known to be inactivated by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were treated with the DNMT inhibitor zebularine. Expression changes of total RNA from treated and untreated cells were compared using an RNA expression microarray. Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of paired normal and tumor tissues of prostate cancer patients. SARS was found to be downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold standard for promoter hypermethylation-inactivated genes in prostate cancer (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive Spearman correlations were found between these genes. SARS was discovered to be a novel gene that is repressed in prostate cancer and could therefore be recommended for its involvement in prostate carcinogenesis.
机译:由于启动子异常甲基化,转录沉默是癌细胞中基因失活的常见机制。使用去甲基化剂重新表达转录沉默基因的功能性表观遗传学筛选可能会鉴定出这种失活的基因,需要进一步评估。我们的目标是鉴定迄今为止未知在前列腺癌中被启动子高甲基化灭活的基因。用DNMT抑制剂zebularine处理DU-145和LNCaP细胞。使用RNA表达微阵列比较了处理过的细胞和未处理过的细胞中总RNA的表达变化。通过RT-qPCR对50例前列腺癌患者正常和肿瘤组织配对的基因上调了2倍以上。发现42/50例前列腺癌中SARS被下调(84%)。此外,GADD45A和SPRY4的表达显着降低(分别为88%和74%)。 90%的患者样品中抑制了前列腺癌中启动子高甲基化失活基因的金标准(GSTP1)。 ROC分析报告了SARS,GADD45A和GSTP1中具有统计意义的AUC曲线,并且在这些基因之间发现了正Spearman相关性。发现SARS是在前列腺癌中被抑制的新基因,因此可以推荐其参与前列腺癌的发生。

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