The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells.

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-26 DOI:10.3390/ph15111319

Mikhlid H Almutairi, Turki M Alrubie, Bader O Almutairi, Abdullah M Alamri, Abdulwahed F Alrefaei, Maha M Arafah, Mohammad Alanazi, Abdelhabib Semlali

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引用次数: 2

Abstract

Background: The expression of human germline genes is restricted to the germ cells of the gonads, which produce sperm and eggs. The germline genes involved in testis development and potentially activated in cancer cells are known as cancer-testis (CT) genes. These genes are potential therapeutic targets and biomarkers, as well as drivers of the oncogenic process. CT genes can be reactivated by treatment with drugs that demethylate DNA. The majority of the existing literature on CT gene activation focuses on X-chromosome-produced CT genes. We tested the hypothesis that epigenetic landscape changes, such as DNA methylation, can alter several CT gene expression profiles in cancer and germ cells.

Methods: Colon cancer (CC) cell lines were treated with the DNA methyltransferase inhibitor (DNMTi) 5-aza-2'-deoxycytidine, or with the histone deacetylase inhibitor (HDACi) trichostatin A (TSA). The effects of these epigenetic treatments on the transcriptional activation of previously published CT genes (CTAG1A, SCP2D1, TKTL2, LYZL6, TEX33, and ACTRT1) and testis-specific genes (NUTM1, ASB17, ZSWIM2, ADAM2, and C10orf82) were investigated.

Results: We found that treatment of CC cell lines with 5-aza-2'-deoxycytidine or TSA correlated with activation of X-encoded CT genes and non-X-encoded CT genes in somatic (non-germline) cells.

Conclusion: These findings confirm that a subset of CT genes can be regulated by hypomethylating drugs and subsequently provide a potential therapeutic target for cancer.

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表观遗传药物在结肠癌细胞中诱导人癌睾丸基因的表达模式

背景:人类生殖系基因的表达仅限于生殖腺的生殖细胞，生殖腺产生精子和卵子。参与睾丸发育并可能在癌细胞中激活的生殖系基因被称为癌睾丸(CT)基因。这些基因是潜在的治疗靶点和生物标志物，也是致癌过程的驱动因素。CT基因可以通过脱氧DNA的药物治疗而重新激活。现有的关于CT基因激活的文献大多集中在x染色体产生的CT基因上。我们测试了表观遗传景观变化的假设，例如DNA甲基化，可以改变癌症和生殖细胞中的几种CT基因表达谱。方法:用DNA甲基转移酶抑制剂(DNMTi) 5-aza-2'-脱氧胞苷或组蛋白去乙酰化酶抑制剂(HDACi)曲古霉素A (TSA)处理结肠癌(CC)细胞株。研究了这些表观遗传处理对先前发表的CT基因(CTAG1A、SCP2D1、TKTL2、LYZL6、TEX33和ACTRT1)和睾丸特异性基因(NUTM1、ASB17、ZSWIM2、ADAM2和C10orf82)转录激活的影响。结果:我们发现用5-aza-2'-脱氧胞苷或TSA处理CC细胞系与体细胞(非生殖系)中x编码的CT基因和非x编码的CT基因的激活相关。结论:这些发现证实了CT基因的一个子集可以通过低甲基化药物来调节，从而为癌症提供了一个潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Pharmaceuticals (Basel, Switzerland)

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