ArticleCancer prevention research (Philadelphia, Pa.)2014
Epigenetic DNA methylation of antioxidative stress regulator NRF2 in human prostate cancer.
Article in Cancer prevention research (Philadelphia, Pa.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 79 citations in OpenAlex.
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- Epigenetic Mechanisms Governing Nrf2 Expression and Its Role in Ferroptosis.Biomedicines · 2025Review
- Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals.Pharmaceutical research · 2025Review
- Application of Metabolomics in Carcinogenesis and Cancer Prevention by Dietary Phytochemicals.Current pharmacology reports · 2025Review
- Pterostilbene Reverses Epigenetic Silencing of Nrf2 and Enhances Antioxidant Response in Endothelial Cells in Hyperglycemic Microenvironment.Nutrients · 2024Article
- Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids.Stem cell reports · 2023Article
- Effects and Mechanisms of Non-Thermal Plasma-Mediated ROS and Its Applications in Animal Husbandry and Biomedicine.International journal of molecular sciences · 2023Review
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- Review
- Uncovering the Secrets of Prostate Cancer's Radiotherapy Resistance: Advances in Mechanism Research.Biomedicines · 2023Review
- Epigenetic effects of herbal medicine.Clinical epigenetics · 2023Review
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.Molecules (Basel, Switzerland) · 2022Review
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia-reperfusion injury.Theranostics · 2022Review
- Neferine improves oxidative stress and apoptosis in benign prostate hyperplasia via Nrf2-ARE pathway.Redox report : communications in free radical research · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Epigenetic control of NRF2, a master regulator of many critical antioxidative stress defense genes in human prostate cancer (CaP), is unknown. Our previous animal study found decreased Nrf2 expression through promoter CpG methylation/histone modifications during prostate cancer progression in TRAMP mice. In this study, we evaluated CpG methylation of human NRF2 promoter in 27 clinical prostate cancer samples and in LNCaP cells using MAQMA analysis and bisulfite genomic DNA sequencing. Prostate cancer tissue microarray (TMA) containing normal and prostate cancer tissues was studied by immunohistochemistry. Luciferase reporter assay using specific human NRF2 DNA promoter segments and chromatin immunoprecipitation (ChIP) assay against histone modifying proteins were performed in LNCaP cells. Three specific CpG sites in the NRF2 promoter were found to be hypermethylated in clinical prostate cancer samples (BPH<ADT-RCaP<AS-CaP). NRF2 staining in human prostate cancer TMA showed a decreasing trend for both intensity and percentage of positive cells from normal tissues to advanced-stage prostate cancer (Gleason score from 3-9). Reporter assays in the LNCaP cells containing these three CpG sites showed methylation-inhibited transcriptional activity of the NRF2 promoter. LNCaP cells treated with 5-aza/TSA restored the expression of NRF2 and NRF2 downstream target genes, decreased expression levels of DNMT and HDAC proteins, and ChIP assays showed increased RNA Pol II and H3Ac with a concomitant decrease in H3K9me3, MBD2, and MeCP2 at CpG sites of human NRF2 promoter. Taken together, these findings suggest that epigenetic modification may contribute to the regulation of transcription activity of NRF2, which could be used as prevention and treatment target of human prostate cancer.
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