ArticleBMC molecular biology2010
Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cells.
Article in BMC molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 84 citations in OpenAlex.
- Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals.Pharmaceutical research · 2025Review
- The role of UGT1A1 polymorphism in the management of colorectal cancer.Oncology reviews · 2025Review
- Whole Transcriptome-Based ceRNA Regulatory Network Analysis of Radiation-Induced Esophageal Epithelial Cell Injury.Biologics : targets & therapy · 2025Article
- Mechanism of 5-fluorouracil induced resistance and role of piperine and curcumin as chemo-sensitizers in colon cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Multiomics dynamic learning enables personalized diagnosis and prognosis for pancancer and cancer subtypes.Briefings in bioinformatics · 2023Article
- An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.NPJ systems biology and applications · 2023Article
- Review
- The Uridine diphosphate (UDP)-glycosyltransferases (UGTs) superfamily: the role in tumor cell metabolism.Frontiers in oncology · 2022Review
- Epigenetics and microRNAs in UGT1As.Human genomics · 2021Review
- HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1.Scientific reports · 2021Article
- Regulation of Nrf2 signaling pathway in heart failure: Role of extracellular vesicles and non-coding RNAs.Free radical biology & medicine · 2021Review
- Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells.Journal of Cancer · 2021Article
- Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology.Journal of cellular and molecular medicine · 2019Article
- Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer.Antioxidants (Basel, Switzerland) · 2019Review
- The role of insulin in transdifferentiated hepatocyte proliferation and function in serum-free medium.Journal of cellular and molecular medicine · 2019Article
- Emerging targets in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Review
- Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.Epigenetics & chromatin · 2018Article
- Regulation of Hepatic UGT2B15 by Methylation in Adults of Asian Descent.Pharmaceutics · 2018Article
- Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity.International journal of environmental research and public health · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundUDP-glucuronosyltransferase 1A1 (UGT1A1) is a pivotal enzyme involved in metabolism of SN-38, the active metabolite of irinotecan commonly used to treat metastatic colorectal cancer. We previously demonstrated aberrant methylation of specific CpG dinucleotides in UGT1A1-negative cells, and revealed that methylation state of the UGT1A1 5'-flanking sequence is negatively correlated with gene transcription. Interestingly, one of these CpG dinucleotides (CpG -4) is found close to a HNF1 response element (HRE), known to be involved in activation of UGT1A1 gene expression, and within an upstream stimulating factor (USF) binding site.
resultsGel retardation assays revealed that methylation of CpG-4 directly affect the interaction of USF1/2 with its cognate sequence without altering the binding for HNF1-alpha. Luciferase assays sustained a role for USF1/2 and HNF1-alpha in UGT1A1 regulation in colon cancer cells. Based on the differential expression profiles of HNF1A gene in colon cell lines, we also assessed whether methylation affects its expression. In agreement with the presence of CpG islands in the HNF1A promoter, treatments of UGT1A1-negative HCT116 colon cancer cells with a DNA methyltransferase inhibitor restore HNF1A gene expression, as observed for UGT1A1.
conclusionsThis study reveals that basal UGT1A1 expression in colon cells is positively regulated by HNF1-alpha and USF, and negatively regulated by DNA methylation. Besides, DNA methylation of HNF1A could also play an important role in regulating additional cellular drug metabolism and transporter pathways. This process may contribute to determine local inactivation of drugs such as the anticancer agent SN-38 by glucuronidation and define tumoral response.
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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 Socratic graph.