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The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells
Mikhlid H Almutairi1, Turki M Alrubie1, Bader O Almutairi1
1Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
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.
Insights
Epigenetic drugs like 5-aza-2'-deoxycytidine and trichostatin A can activate cancer-testis (CT) genes in colon cancer cells. This finding highlights CT genes as potential therapeutic targets for cancer treatment.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Human germline genes are normally restricted to sperm and egg production.
- Cancer-testis (CT) genes, involved in testis development, can be activated in cancer cells.
- Epigenetic alterations, particularly DNA methylation, influence CT gene expression.
Purpose of the Study:
- To investigate the impact of epigenetic modifications on CT gene expression in cancer.
- To test if DNA methylation changes can alter CT gene profiles in cancer and germ cells.
Main Methods:
- Colon cancer cell lines were treated with DNA methyltransferase inhibitor (DNMTi) 5-aza-2 -deoxycytidine.
- Colon cancer cell lines were treated with histone deacetylase inhibitor (HDACi) trichostatin A (TSA).
- Transcriptional activation of specific CT and testis-specific genes was analyzed post-treatment.
Main Results:
- Treatment with 5-aza-2 -deoxycytidine or TSA activated X-encoded CT genes in colon cancer cells.
- Epigenetic treatments also led to the activation of non-X-encoded CT genes in somatic cells.
- The study observed CT gene activation in non-germline cells following epigenetic drug treatment.
Conclusions:
- A subset of CT genes are regulated by hypomethylating drugs.
- Activated CT genes represent a potential therapeutic target for cancer treatment.
- Epigenetic regulation of CT genes offers new avenues for cancer therapy.
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