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人类癌-睾丸基因的表达模式通过表观遗传药物在结肠癌细胞中被诱导。

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

作者信息

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

机构信息

Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Pharmaceuticals (Basel). 2022 Oct 26;15(11):1319. doi: 10.3390/ph15111319.

DOI:10.3390/ph15111319
PMID:36355490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9692864/
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 (, , , , , and ) and testis-specific genes (, , , , and ) 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.

摘要

背景

人类种系基因的表达仅限于性腺的生殖细胞，性腺产生精子和卵子。参与睾丸发育并可能在癌细胞中被激活的种系基因被称为癌-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基因可以通过用使DNA去甲基化的药物治疗而重新激活。现有的关于CT基因激活的大多数文献都集中在X染色体产生的CT基因上。我们测试了这样一个假设，即表观遗传景观变化，如DNA甲基化，可以改变癌症和生殖细胞中几种CT基因的表达谱。

方法

用DNA甲基转移酶抑制剂（DNMTi）5-氮杂-2'-脱氧胞苷或组蛋白脱乙酰酶抑制剂（HDACi）曲古抑菌素A（TSA）处理结肠癌细胞系。研究了这些表观遗传处理对先前发表的CT基因（、、、、、和）和睾丸特异性基因（、、、、和）转录激活的影响。

结果

我们发现用5-氮杂-2'-脱氧胞苷或TSA处理结肠癌细胞系与体细胞（非生殖细胞）中X编码的CT基因和非X编码的CT基因的激活相关。

结论

这些发现证实了一部分CT基因可以通过低甲基化药物进行调控，从而为癌症提供了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/bec73d0897ce/pharmaceuticals-15-01319-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/1879f1e1912e/pharmaceuticals-15-01319-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/61f61f6ff517/pharmaceuticals-15-01319-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/da81d818b86c/pharmaceuticals-15-01319-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/eec0ed03d07a/pharmaceuticals-15-01319-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/5e38fdb6a6d5/pharmaceuticals-15-01319-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/49156d5ca76b/pharmaceuticals-15-01319-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/cdef9e9ea983/pharmaceuticals-15-01319-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/bec73d0897ce/pharmaceuticals-15-01319-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/1879f1e1912e/pharmaceuticals-15-01319-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/61f61f6ff517/pharmaceuticals-15-01319-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/da81d818b86c/pharmaceuticals-15-01319-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/eec0ed03d07a/pharmaceuticals-15-01319-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/5e38fdb6a6d5/pharmaceuticals-15-01319-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/49156d5ca76b/pharmaceuticals-15-01319-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/cdef9e9ea983/pharmaceuticals-15-01319-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb46/9692864/bec73d0897ce/pharmaceuticals-15-01319-g008.jpg

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Genes (Basel). 2022 May 1;13(5):807. doi: 10.3390/genes13050807.
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Overexpression of gene in Saudi colon cancer patients.沙特结肠癌患者中基因的过表达。
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The Cancer/Testis Antigen Gene Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors.
Higher Expression Levels of and in Patients with Colon Cancer: Regulated In Vitro by the Inhibition of Methylation and Histone Deacetylation.结肠癌患者中 和 的表达水平升高：通过抑制甲基化和组蛋白去乙酰化体外调控。
Medicina (Kaunas). 2023 May 20;59(5):988. doi: 10.3390/medicina59050988.
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