The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells
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 tar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/11/1319 |
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| author | Mikhlid H. Almutairi Turki M. Alrubie Bader O. Almutairi Abdullah M. Alamri Abdulwahed F. Alrefaei Maha M. Arafah Mohammad Alanazi Abdelhabib Semlali |
| author_facet | Mikhlid H. Almutairi Turki M. Alrubie Bader O. Almutairi Abdullah M. Alamri Abdulwahed F. Alrefaei Maha M. Arafah Mohammad Alanazi Abdelhabib Semlali |
| author_sort | Mikhlid H. Almutairi |
| collection | DOAJ |
| description | 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 (<i>CTAG1A</i>, <i>SCP2D1</i>, <i>TKTL2</i>, <i>LYZL6</i>, <i>TEX33</i>, and <i>ACTRT1</i>) and testis-specific genes (<i>NUTM1</i>, <i>ASB17</i>, <i>ZSWIM2</i>, <i>ADAM2</i>, and <i>C10orf82</i>) 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. |
| first_indexed | 2024-03-09T18:45:10Z |
| format | Article |
| id | doaj.art-8d0a5153a937437daf3c616f62706f14 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T18:45:10Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-8d0a5153a937437daf3c616f62706f142023-11-24T06:17:59ZengMDPI AGPharmaceuticals1424-82472022-10-011511131910.3390/ph15111319The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer CellsMikhlid H. Almutairi0Turki M. Alrubie1Bader O. Almutairi2Abdullah M. Alamri3Abdulwahed F. Alrefaei4Maha M. Arafah5Mohammad Alanazi6Abdelhabib Semlali7Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaZoology Department, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaZoology Department, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaZoology Department, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaPathology Department, College of Medicine, King Saud University, Riyadh 11451, Saudi ArabiaGenome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaGroupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de la Terrasse, Local 1758, Québec, QC G1V 0A6, CanadaBackground: 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 (<i>CTAG1A</i>, <i>SCP2D1</i>, <i>TKTL2</i>, <i>LYZL6</i>, <i>TEX33</i>, and <i>ACTRT1</i>) and testis-specific genes (<i>NUTM1</i>, <i>ASB17</i>, <i>ZSWIM2</i>, <i>ADAM2</i>, and <i>C10orf82</i>) 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.https://www.mdpi.com/1424-8247/15/11/1319cancer-testis (CT) geneDNA methyl-transferase inhibitor (DNMTi)histone deacetylase inhibitor (HDACi)immunotherapycolon cancer |
| spellingShingle | Mikhlid H. Almutairi Turki M. Alrubie Bader O. Almutairi Abdullah M. Alamri Abdulwahed F. Alrefaei Maha M. Arafah Mohammad Alanazi Abdelhabib Semlali The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells Pharmaceuticals cancer-testis (CT) gene DNA methyl-transferase inhibitor (DNMTi) histone deacetylase inhibitor (HDACi) immunotherapy colon cancer |
| title | The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells |
| title_full | The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells |
| title_fullStr | The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells |
| title_full_unstemmed | The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells |
| title_short | The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells |
| title_sort | expression patterns of human cancer testis genes are induced through epigenetic drugs in colon cancer cells |
| topic | cancer-testis (CT) gene DNA methyl-transferase inhibitor (DNMTi) histone deacetylase inhibitor (HDACi) immunotherapy colon cancer |
| url | https://www.mdpi.com/1424-8247/15/11/1319 |
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