白细胞介素 6 的 DNA 甲基化作为早期检测结直肠癌的生物标志物

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL Journal of Contemporary Medical Sciences Pub Date : 2023-12-26 DOI:10.22317/jcms.v9i6.1440
Sakar Ahmed Abdullah, Dlnya Assad Mohamad
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引用次数: 0

摘要

研究目的确定结直肠癌患者和结直肠多发性硬化患者白细胞介素6启动子区域的DNA甲基化模式,以作为早期检测结直肠癌的生物标志物。 方法:为此,我们使用亚硫酸氢盐转换测序法检测了九十份样本(对照组、癌症患者和结直肠息肉样本各三十份)中 IL6 启动子区的 DNA 甲基化模式,具体为 358 bp(-292 至 +67),包括 7 个 CpG 位点(-228、-213、-163、-119、+10、+19、+25)。 结果结果表明,CpG +25 和 CpG -119 可作为早期检测结肠癌的生物标志物,CpG +25 和 CpG-119 的 P 值分别为 0.001 和 0.004,差异显著。癌症组中 CpG -119 的低甲基化有利于甲基敏感转录因子 Sp1 的结合。除了 CpG +25 的高甲基化阻止了甲基敏感的绝缘体 CTF 的结合外,它还增强了 IL6 的过表达,解除了绝缘体与癌症样本启动子区域的结合,使启动子区域向 TFs 开放,从而增强了过表达。此外,在 98.6% 的入组样本中,还观察到 CpG -228 处有一个显著的未记录 SNP。 结论在 DNA 甲基化状态下,由于 CpG +25 和 CpG -119 存在显著的甲基化水平,IL 6 可能会导致大肠息肉和大肠息肉癌的发生。
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The DNA methylation of the interleukin6 as a biomarker for the early detection of colorectal cancer
Objectives: To identify the DNA methylation pattern of the interleukin6 promoter region in colorectal cancer patients and colorectal polys patients that could be a biomarker for early detection of colorectal cancer. Methods: For this purpose, we examined the DNA methylation pattern of the promoter region of the IL6 specifically 358 bp (-292 to +67) including 7 CpG sites (-228, -213, -163, -119, +10, +19, +25) in a total of ninety samples with thirty samples each for controls, cancer patients, and colorectal polyps using the bisulfite conversion sequencing method. Result: Our results indicate that CpG +25 and CpG -119 can serve as biomarkers for early detection of colon cancer, showing a significant difference in P-values of 0.001 at CpG +25 and 0.004 at CpG-119. The hypomethylation of CpG -119 in cancer groups facilitates the binding of the methyl-sensitive transcription factor Sp1. It enhances the overexpression of IL6 besides hypermethylation of CpG +25 that prevents binding of the methyl-sensitive insulator CTF, unbinding the insulator to the promoter region of the cancer samples makes the promoter region open access to the TFs that enhances overexpression. Furthermore, a remarkable non-recorded SNP at CpG -228 was observed in 98.6% of the enrolled groups. Conclusion: In the state of DNA methylation, IL 6 could contribute to the onset of colorectal polyps and colorectal polyps cancer due to a significant level of methylation in CpG +25 and CpG -119.
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来源期刊
Journal of Contemporary Medical Sciences
Journal of Contemporary Medical Sciences MEDICINE, GENERAL & INTERNAL-
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审稿时长
12 weeks
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