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DNA hypermethylation of SHISA3 as a mechanism of gene inactivation and as a novel prognostic biomarker in colorectal cancer.
Journal of Clinical Oncology ( IF 42.1 ) Pub Date : 2015-05-20 , DOI: 10.1200/jco.2015.33.15_suppl.e14532
Chun-Chieh Chen, Ming-Hong Tsai, Wen-Chi Chen, Sung-Liang Yu, Tzu-Ming Jao, Chi-Yan Huang, Sheng-Tai Tzeng, Sou-Jhy Yen, Ya-Chien Yang

e14532 Background: Shisa3, a newly identified tumor suppressor, inhibits tumorigenesis and metastasis via counter-regulation of β-catenin in non-small cell lung cancer. However, its tumor suppressor role in other human cancers and the mechanism of gene inactivation still remain unknown. Methods: We validated the expression of SHISA3 gene by qRT-PCR. Then, we treated CRC cell lines with 5-aza-2’-deoxycytidine (5-Aza-CdR) and carried out bisulfate sequencing PCR and pyrosequencing in paired colorectal tumor and normal mucosa tissues to assess the DNA methylation status of SHISA3 gene. Results: We found that SHISA3 expression was significantly down-regulated in 34 (65.4%) of 52 colorectal carcinomas compared with corresponding normal mucosae by qRT-PCR. To explore the epigenetic silencing of SHISA3 gene, CRC cells were treated with DNA methylation inhibitor 5-Aza-CdR, and SHISA3 expression was obviously induced in four (66.7%) of six cell lines. CpG islands spanning SHISA3 gene were predicted via MethPrimer ...

中文翻译:

SHISA3 的 DNA 高甲基化作为基因失活的机制和结直肠癌的新型预后生物标志物。

e14532 背景:Shisa3 是一种新发现的肿瘤抑制因子,通过反调节非小细胞肺癌中的 β-连环蛋白来抑制肿瘤发生和转移。然而,其在其他人类癌症中的抑癌作用和基因失活的机制仍然未知。方法:我们通过 qRT-PCR 验证了 SHISA3 基因的表达。然后,我们用 5-aza-2'-脱氧胞苷 (5-Aza-CdR) 处理 CRC 细胞系,并在配对的结直肠肿瘤和正常粘膜组织中进行硫酸氢盐测序 PCR 和焦磷酸测序,以评估 SHISA3 基因的 DNA 甲基化状态。结果:我们通过 qRT-PCR 发现,与相应的正常粘膜相比,52 例结直肠癌中有 34 例(65.4%)的 SHISA3 表达显着下调。为了探索 SHISA3 基因的表观遗传沉默,CRC 细胞用 DNA 甲基化抑制剂 5-Aza-CdR 处理,在 6 个细胞系中的 4 个(66.7%)中明显诱导了 SHISA3 表达。通过 MethPrimer 预测跨越 SHISA3 基因的 CpG 岛...
更新日期:2015-05-20
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