ArticleScientific reports2020
Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- TET1 modulates trophoblast function by regulation of ODC1 in preeclampsia.Scientific reports · 2025Article
- Untangling the Uncertain Role of Overactivation of the Renin-Angiotensin-Aldosterone System with the Aging Process Based on Sodium Wasting Human Models.International journal of molecular sciences · 2024Review
- The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis.iScience · 2024Article
- Discovery of novel DNA methylation biomarker panels for the diagnosis and differentiation between common adenocarcinomas and their liver metastases.Scientific reports · 2024Article
- Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.Cancer cell · 2023Article
- Consistent DNA Hypomethylations in Prostate Cancer.International journal of molecular sciences · 2022Article
- Differential DNA Methylation of THOR andCancers · 2022Article
- Guest Edited Collection: Epigenetics within the tumor microenvironment.Scientific reports · 2022Article
- Methyl Group Metabolism in Differentiation, Aging, and Cancer.International journal of molecular sciences · 2022Review
- Article
- Epigenetics in the Diagnosis and Therapy of Malignant Melanoma.International journal of molecular sciences · 2022Review
- Many Different LINE-1 Retroelements Are Activated in Bladder Cancer.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urothelial carcinoma (UC) is a common disease causing significant morbidity and mortality as well as considerable costs for health systems. Extensive aberrant methylation of DNA is broadly documented in early UC, contributing to genetic instability, altered gene expression and tumor progression. However the triggers initiating aberrant methylation are unknown. Recently we discovered that several genes encoding key enzymes of methyl group and polyamine metabolism, including Ornithine Decarboxylase 1 (ODC1), are affected by DNA methylation in early stage UC. In this study, we investigated the hypothesis that these epigenetic alterations act in a feed-forward fashion to promote aberrant DNA methylation in UC. We demonstrate that siRNA-mediated knockdown of ODC1 expression elicits genome-wide LINE-1 demethylation, induction of LINE-1 transcripts and double-strand DNA breaks and decreases viability in primary cultured uroepithelial cells. Similarly, following siRNA-mediated knockdown of ODC1, UC cells undergo double-strand DNA breaks and apoptosis. Collectively, our findings provide evidence that ODC1 gene hypermethylation could be a starting point for the onset of genome-wide epigenetic aberrations in urothelial carcinogenesis. Furthermore, LINE-1 induction enabled by ODC1 interference provides a new experimental model to study mechanisms and consequences of LINE-1 activation in the etiology and progression of UC as well as presumably other cancers.
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