Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation

作者：Kyoung Ah Kang, Jinny Park, Mei Jing Piao, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Jung-Hwan Kim, Suk Ju Cho, Jin Won Hyun · 发表于：Biomolecules & Therapeutics · 年份：2024 · DOI：10.4062/biomolther.2024.183 · 被引用次数：4 · 研究领域：Epigenetics and DNA Methylation、FOXO transcription factor regulation、Glutathione Transferases and Polymorphisms

promoter. TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.