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原钙黏蛋白γ亚家族A12和溶质载体家族19 A1启动子的高甲基化促进了结直肠癌的发生和转移。

Hypermethylation of protocadherin γ subfamily A12 and solute carrier family 19 A 1 promoters contributes to the occurrence and metastasis of colorectal cancer.

作者信息

Zhang Cheng, Li Jinyun, Huang Tao, Chen Cheng, Hong Qingxiao, Ji Huihui, Ye Meng, Duan Shiwei

机构信息

Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.

Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.

出版信息

Oncol Lett. 2018 Jun;15(6):8215-8222. doi: 10.3892/ol.2018.8393. Epub 2018 Mar 30.

DOI:10.3892/ol.2018.8393
PMID:29805555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5950180/
Abstract

The development of colorectal cancer (CRC) involves genetic and epigenetic modifications, and aberrant DNA methylation within gene promoters is a primary mediator of epigenetic inheritance in CRC. The present study evaluated whether promoter methylation of four CRC candidate genes [protocadherin γ subfamily A12 (-γ-), solute carrier family 19 A 1 (), cAMP responsive element binding protein () and cylindromatosis () contributed to the risk and metastasis of CRC by screening a total of 42 CRC and 42 adjacent normal tissue samples. DNA methylation was measured by methylation-specific polymerase chain reaction (MSP). Polymerase chain reaction (PCR) products were bisulfite converted and validated by sequencing. The χ test was employed to assess the association between promoter methylation and a series of clinicopathological characteristics. The promoters of -γ- and were observed to be more frequently methylated in CRC tissues than normal tissues. In addition, significantly higher methylation of the -γ- and promoters was also observed in CRC tissues with lymph metastasis compared with those without lymph metastasis. In addition, no association was observed between and methylation and the occurrence and metastasis of CRC. These results suggest that the hypermethylation of the -γ- and promoters may contribute to the occurrence and metastasis of CRC in the Han Chinese population.

摘要

结直肠癌(CRC)的发生涉及基因和表观遗传修饰,基因启动子内异常的DNA甲基化是CRC表观遗传遗传的主要介导因素。本研究通过筛查总共42例CRC组织和42例相邻正常组织样本,评估了四个CRC候选基因[原钙黏蛋白γ亚家族A12(-γ-)、溶质载体家族19 A 1()、环磷酸腺苷反应元件结合蛋白()和圆柱瘤蛋白()]的启动子甲基化是否会导致CRC的风险和转移。通过甲基化特异性聚合酶链反应(MSP)测量DNA甲基化。聚合酶链反应(PCR)产物经亚硫酸氢盐转化并通过测序验证。采用χ检验评估启动子甲基化与一系列临床病理特征之间的关联。观察到CRC组织中-γ-和的启动子甲基化频率高于正常组织。此外,与无淋巴结转移的CRC组织相比,有淋巴结转移的CRC组织中-γ-和启动子的甲基化也显著更高。此外,未观察到和甲基化与CRC的发生和转移之间存在关联。这些结果表明,-γ-和启动子的高甲基化可能有助于汉族人群中CRC的发生和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/5950180/ede7c52fbcbe/ol-15-06-8215-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/5950180/1a6416b60489/ol-15-06-8215-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/5950180/ede7c52fbcbe/ol-15-06-8215-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/5950180/1a6416b60489/ol-15-06-8215-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/5950180/ede7c52fbcbe/ol-15-06-8215-g01.jpg

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Meta-analyses of methylation markers for prostate cancer.前列腺癌甲基化标志物的Meta分析。
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