编码卵巢癌和乳腺癌推定癌蛋白的人EEF1A2基因CpG岛分布的计算分析

P. Dharmasaroja
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引用次数: 0

摘要

组织特异性翻译延伸因子eEF1A2最近被证明是一种在人类卵巢癌和乳腺癌中过度表达的潜在癌蛋白。编码在20号染色体上的eEF1A2与编码在6号染色体上的密切相关的eEF1A1具有相似的特征。目前尚不清楚为什么组织特异性eEF1A2在eEF1A1已经高水平存在的组织中具有致癌特性。CpG岛的异常甲基化可导致基因表达的改变,从而导致癌症的生长和转移。本研究采用最新发展的更严格的CpG岛标准,即DNA序列长度大于500 bp, G + C含量等于或大于55%,CpG/期望CpG为0.65,分析了EEF1A1和EEF1A2的CpG岛分布。根据这些标准,在EEF1A1中鉴定出两个CpG岛:一个具有位于启动子区域的Alu重复序列,另一个没有Alus,它们跨越外显子1和外显子2并重叠转录起始位点。相比之下,EEF1A2的四个CpG岛中有三个位于外显子区域(外显子3,4,7和8),并且没有一个与转录起始位点重叠。在EEF1A1和EEF1A2中,CpG岛的数量和分布的差异,包括Alu重复序列的存在或不存在,可能解释了它们在某些癌细胞中的差异表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Computational Analysis of CpG Island Distribution in Human EEF1A2 Gene Encoding a Putative Oncoprotein Implicated in Ovarian and Breast Cancer
The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncoprotein that is over expressed in human ovarian and breast cancer. eEF1A2 encoded on chromosome 20 shares similar features to the near-ubiquitously expressed eEF1A1, a closely-related isoform encoded on chromosome 6. It is still unknown why the tissue-specific eEF1A2 should have oncogenic properties in tissues in which eEF1A1 is already present at high levels. Abnormal methylation of CpG islands can lead to changes in expression of genes resulting in cancer growth and metastasis. In the present study, recently-developed and more stringent criteria for CpG islands, as being a DNA sequence longer than 500 bp with a G + C content equal to or greater than 55% and observed CpG/expected CpG of 0.65, were used to analyze CpG islands distribution in EEF1A1 and EEF1A2. Under these criteria, two CpG islands were identified in EEF1A1: one with an Alu repeat located in the promoter region and one without Alus, which spanned exon 1 and exon 2 and overlapped the transcription start site. In contrast, three out of four CpG islands in EEF1A2 were located in the exonic regions (exons 3, 4, 7 and 8), and none of them overlapped the transcription start site. Differences in the number and distribution of CpG islands, including the presence or absence of Alu repeats, in EEF1A1 and EEF1A2 may explain their differential expressions in certain cancer cells.
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