ArticleSignal transduction and targeted therapy2023
Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Dual Compartmentalization of GSTA4 Suppresses Ferroptosis to Drive Antiandrogen Resistance in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A prostate cancer-specific super-enhancer at 1q42.3 regulates the CAPN2 and KRT19.The Journal of biological chemistry · 2026Article
- Metabolic convergence of diabetes and prostate cancer: from dysglycemia to tumor microenvironment reprogramming.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Radiotherapy followed by metformin neoadjuvant therapy drives superior pancreatic cancer ferroptosis and augments anti-tumor immunity.Fundamental research · 2026Article
- Integrated Transcriptomic Analysis Identifies Potential Biomarkers in Castration-Resistant Prostate Cancer.World journal of oncology · 2026Article
- Metformin in prostate cancer: a context-dependent antitumour strategy driven by metabolic vulnerability and signalling network.Discover oncology · 2026Review
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression.Cancer medicine · 2026Article
- Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Manipulating the cGAS-STING Axis: advancing innovative strategies for osteosarcoma therapeutics.Frontiers in immunology · 2025Review
- Super-enhancer inhibitors THZ2 and JQ1 reverse temozolomide resistance in glioblastoma by suppressing SE-driven SOX9 expression.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- The Impact of Diabetes and Antidiabetics on Uro-Oncological Disease Outcomes: A Single-Center Experience.Urologia internationalis · 2025Article
- Assessing expression patterns of PTGR1, a potential biomarker for acylfulven sensitivity in urothelial carcinoma.Scientific reports · 2024Article
- Article
- NUCB2 promotes hepatocellular carcinoma cell growth and metastasis by activating the E2F4/PTGR1 axis.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing. Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases, resulting in reduced sensitivity to metformin. Additionally, we identified key transcription factors that significantly increase PTGR1 expression, such as SRF and RUNX3, providing potential new targets to address metformin resistance in PCa. In conclusion, our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis, offering potential avenues to enhance metformin's therapeutic efficacy in PCa.
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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.