ArticleOncology letters2015
Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells.
Article in Oncology letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04366479 (Effect of Endurance Exercise on nrf2 mRNA Expression Gene and Physical Fitness), which is not on this map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Endurance Exercise on nrf2 mRNA Expression Gene and Physical Fitness (VO2max) of Indonesian Hajj Health Officers
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review.PloS one · 2017Pooled it
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- Involvement of the DNA Demethylase Thymine DNA Glycosylase in Anticancer Drug Resistance.Biomolecules & therapeutics · 2025Article
- Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2024Review
- NFR2/ABC transporter axis in drug resistance of breast cancer cells.Molecular biology reports · 2023Review
- Effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on NRF2, KEAP1, SOD1, and GPX2 expression in human colorectal cancer cell lines.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Epigenomic reprogramming of therapy-resistant circulating tumor cells in colon cancer.Frontiers in cell and developmental biology · 2023Article
- Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer.Cancer letters · 2022Article
- Clinical Significance of Heme Oxygenase 1 in Tumor Progression.Antioxidants (Basel, Switzerland) · 2021Review
- Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.Molecules (Basel, Switzerland) · 2021Review
- Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.Cancers · 2020Review
- 5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes.Cancer science · 2020Review
- Evaluation of the Epigenetic Demethylation of NRF2, a Master Transcription Factor for Antioxidant Enzymes, in Colorectal Cancer.Reports of biochemistry & molecular biology · 2020Article
- Demethylation of the NRF2 Promoter Protects Against Carcinogenesis Induced by Nano-SiOFrontiers in genetics · 2020Article
- Role of DNA Methylation in the Resistance to Therapy in Solid Tumors.Frontiers in oncology · 2020Review
- DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer.Cell death and differentiation · 2019Article
- Can Nrf2 Modulate the Development of Intestinal Fibrosis and Cancer in Inflammatory Bowel Disease?International journal of molecular sciences · 2019Review
- Potential Applications of NRF2 Inhibitors in Cancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells.Journal of cellular biochemistry · 2018Article
- Role of NRF2 in protection of the gastrointestinal tract against oxidative stress.Journal of clinical biochemistry and nutrition · 2018Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET)1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.