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Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors
Ist Teil von
Epigenetics, 2024-12, Vol.19 (1), p.2309824
Ort / Verlag
United States: Taylor & Francis
Erscheinungsjahr
2024
Quelle
Taylor & Francis Journals Auto-Holdings Collection
Beschreibungen/Notizen
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
and
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
and
genes.
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
, and several
genes. We confirmed changes in
and
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
and
genes may influence chemosensitivity and may need to be considered during chemotherapy.