Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors
Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug t...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Epigenetics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2024.2309824 |
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| author | Julia Krushkal Yingdong Zhao Kyle Roney Weimin Zhu Alan Brooks Deborah Wilsker Ralph E. Parchment Lisa M. McShane James H. Doroshow |
| author_facet | Julia Krushkal Yingdong Zhao Kyle Roney Weimin Zhu Alan Brooks Deborah Wilsker Ralph E. Parchment Lisa M. McShane James H. Doroshow |
| author_sort | Julia Krushkal |
| collection | DOAJ |
| description | Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of HDAC and SIRT genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple HDAC and SIRT genes. HDAC5 was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of HDAC5, HDAC1, and several SIRT genes. We confirmed changes in HDAC and SIRT expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of HDAC and SIRT genes may influence chemosensitivity and may need to be considered during chemotherapy. |
| format | Article |
| id | doaj-art-76cdf0bfff0e453b87e8b5bd10e9b649 |
| institution | OA Journals |
| issn | 1559-2294 1559-2308 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj-art-76cdf0bfff0e453b87e8b5bd10e9b6492025-08-20T02:30:41ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2024.2309824Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitorsJulia Krushkal0Yingdong Zhao1Kyle Roney2Weimin Zhu3Alan Brooks4Deborah Wilsker5Ralph E. Parchment6Lisa M. McShane7James H. Doroshow8Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USABiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USADepartment of Biostatistics and Bioinformatics, George Washington University, Washington, DC, USAClinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USAClinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USAClinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USAClinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USABiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USADivision of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USAHistone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of HDAC and SIRT genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple HDAC and SIRT genes. HDAC5 was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of HDAC5, HDAC1, and several SIRT genes. We confirmed changes in HDAC and SIRT expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of HDAC and SIRT genes may influence chemosensitivity and may need to be considered during chemotherapy.https://www.tandfonline.com/doi/10.1080/15592294.2024.2309824Histone deacetylasesirtuindasatinibchemosensitivityHDAC5 |
| spellingShingle | Julia Krushkal Yingdong Zhao Kyle Roney Weimin Zhu Alan Brooks Deborah Wilsker Ralph E. Parchment Lisa M. McShane James H. Doroshow Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors Epigenetics Histone deacetylase sirtuin dasatinib chemosensitivity HDAC5 |
| title | Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| title_full | Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| title_fullStr | Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| title_full_unstemmed | Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| title_short | Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| title_sort | association of changes in expression of hdac and sirt genes after drug treatment with cancer cell line sensitivity to kinase inhibitors |
| topic | Histone deacetylase sirtuin dasatinib chemosensitivity HDAC5 |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2024.2309824 |
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