ArticlePloS one2021
Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Stress-specific 14-3-3-client modules in digestive cancers: an evidence-graded review of adaptive survival and therapy resistance.Cancer biology & therapy · 2026Review
- Ploidy shapes gemcitabine response through altered potency and delayed cell death.bioRxiv : the preprint server for biology · 2026Article
- Peptides as integrative modulators for clinical prognosis and targeted therapy in pancreatic cancer.Discover oncology · 2026Review
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RRM1 O-GlcNAcylation inhibition suppresses pancreatic cancer via TK1-mediated replication stress.Cancer gene therapy · 2025Article
- MTCH2 regulates NRF2-mediated RRM1 expression to promote melanoma proliferation and dacarbazine insensitivity.Cell death & disease · 2025Article
- Resectable Pancreatic Adenocarcinomas following Neoadjuvant Chemotherapy with Gemcitabine Plus S-1: Two Case Reports of Opposite Oncological Outcomes.Surgical case reports · 2025Article
- Roles of nucleotide metabolism in pancreatic cancer.Frontiers in immunology · 2025Review
- Pan-Cancer Drug Response Prediction Using Integrative Principal Component Regression.Statistics in biosciences · 2024Article
- Initial Low-Dose Hydroxyurea and Anagrelide Combination in Essential Thrombocythemia: Comparable Response with Lower Toxicity.Journal of clinical medicine · 2024Article
- 4'-Ethynyl-2'-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress.Molecular cancer therapeutics · 2024Article
- Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.Cancer chemotherapy and pharmacology · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Molecular Profile of Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2023Review
- RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer.International journal of oncology · 2023Article
- A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach.International journal of molecular sciences · 2023Review
- Proteomic Analysis of the Effect ofMolecules (Basel, Switzerland) · 2022Article
- High Glucose Promotes Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance and Invasion through Modulating ROS/MMP-3 Signaling Pathway.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRRM1 is functionally associated with DNA replication and DNA damage repair. However, the biological activity of RRM1 in pancreatic cancer remains undetermined.
methodsTo determine relationships between RRM1 expression and the prognosis of pancreatic cancer, and to explore RRM1 function in cancer biology, we investigated RRM1 expression levels in 121 pancreatic cancer patients by immunohistochemical staining and performed in vitro experiments to analyze the functional consequences of RRM1 expression.
resultsPatients with high RRM1 expression had significantly poorer clinical outcomes (overall survival; p = 0.006, disease-free survival; p = 0.0491). In particular, high RRM1 expression was also associated with poorer overall survival on adjuvant chemotherapy (p = 0.008). We found that RRM1 expression was increased 24 hours after exposure to gemcitabine and could be suppressed by histone acetyltransferase inhibition. RRM1 activation in response to gemcitabine exposure was induced mainly in the cytoplasm and cytoplasmic RRM1 activation was related to cancer cell viability. In contrast, cancer cells lacking cytoplasmic RRM1 activation were confirmed to show severe DNA damage. RRM1 inhibition with specific siRNA or hydroxyurea enhanced the cytotoxic effects of gemcitabine for pancreatic cancer cells.
conclusionsCytoplasmic RRM1 activation is involved in biological processes related to drug resistance in response to gemcitabine exposure and could be a potential target for pancreatic cancer treatment.
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