Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer
Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer
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DOI：
10.1007/s00432-012-1353-5
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发表时间：
2013-03
影响因子：
3.6
通讯作者：
Xian Zhong;Yongliang Zhu;Jianshan Mao;Jia-wei Zhang;Shu Zheng
中科院分区：
文献类型：
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作者：
Xian Zhong;Yongliang Zhu;Jianshan Mao;Jia-wei Zhang;Shu Zheng
目的DNA甲基化异常在肿瘤细胞中普遍存在。导致肿瘤抑制基因功能丧失的表观遗传学改变经常参与肿瘤的发生和进展。近年来，PCDH 10的甲基化被报道与多种血液系统恶性肿瘤以及一些实体瘤有关。PCDH10基因在大肠癌中是否发生下调尚不清楚。PCDH10再表达的影响，在生长，集落形成，细胞周期，和invasion assays.ResultsIn这项研究中，我们发现，100%（8 8）的大肠癌细胞系沉默PCDH10，但不是正常的大肠上皮细胞。去甲基化处理证实表达降低与启动子甲基化密切相关。PCDH10的高甲基化也检测到85%的原发性结直肠肿瘤，而不是在邻近的正常大肠组织。结论我们的研究结果表明，PCDH10是一个重要的肿瘤抑制基因，具有抑制细胞增殖，克隆形成，并抑制细胞侵袭在结直肠癌的发展中的关键作用。因此，PCDH10甲基化可能是结直肠癌患者的一个有用的生物标志物。
PurposeAberrant DNA methylation is common in cancer cells. Epigenetic alterations resulting in the loss of tumor suppression gene functions are frequently involved in tumor development and progression. Recently, methylation ofPCDH10was reported to be associated with multiple hematologic malignancies as well as some solid tumors. Whether the down-regulation ofPCDH10happens in CRC remains unknown.MethodsMethylation status ofPCDH10was evaluated by methylation-specific PCR analysis. The effects ofPCDH10re-expression were determined in growth, colony formation, cell cycle, and invasion assays.ResultsIn this study, we found that 100 % (8 of 8) of colorectal cancer cell lines were silenced forPCDH10, but not normal colorectal epithelial cells. Demethylation treatment confirmed that the reduced expression is associated closely with promoter methylation. Hyper-methylation ofPCDH10was also detected in 85 % of primary colorectal tumors, but not in adjacent normal colorectal tissues.ConclusionsOur results suggest thatPCDH10is an important tumor suppression gene with key roles of suppressing cell proliferation, clonogenicity, and inhibiting cell invasion in the development of colorectal cancer. Thus,PCDH10methylation may constitute a useful biomarker of colorectal cancer patients.