ArticleCell cycle (Georgetown, Tex.)2014
Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer.Biomedicines · 2026Review
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.Journal of ovarian research · 2026Article
- Proteomic and phenotypic profiling of replicative-senescent human foreskin fibroblasts under brief heat shock.Cell stress & chaperones · 2026Article
- Article
- Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.Future medicinal chemistry · 2025Review
- Ribonucleotide-diphosphate reductase subunit M2 (RRM2) expression and colorectal cancer invasiveness: a potential prognostic biomarker.Molecular biology reports · 2025Article
- Osalmid sensitizes clear cell renal cell carcinoma to navitoclax through a STAT3/BCL-XL pathway.Cancer letters · 2025Article
- Interplay between altered metabolism and DNA damage and repair in ovarian cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- A structure-based designed small molecule depletes hRpn13Nature communications · 2024Article
- The Clinical and Prognostic Significance of Ribonucleotide Reductase Subunits RRM1 and RRM2 mRNA Levels in Patients with Chronic Lymphocytic Leukemia.Clinical hematology international · 2023Article
- Inferring cancer common and specific gene networks via multi-layer joint graphical model.Computational and structural biotechnology journal · 2023Article
- Identification and validation of a ferroptosis-related gene to predict survival outcomes and the immune microenvironment in lung adenocarcinoma.Cancer cell international · 2022Article
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance.Diagnostic pathology · 2022Article
- Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control.Scientific reports · 2021Article
- Article
- Ribonucleotide reductase small subunit M2 is a master driver of aggressive prostate cancer.Molecular oncology · 2020Article
- Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer.Journal of ovarian research · 2020Article
- The Enhanced Tumor Specificity of TG6002, an Armed Oncolytic Vaccinia Virus Deleted in Two Genes Involved in Nucleotide Metabolism.Molecular therapy oncolytics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Epithelial ovarian cancer (EOC) is the leading cause of gynecological-related cancer deaths in the United States. There is, therefore, an urgent need to develop novel therapeutic strategies for this devastating disease. Cellular senescence is a state of stable cell growth arrest that acts as an important tumor suppression mechanism. Ribonucleotide reductase M2 (RRM2) plays a key role in regulating the senescence-associated cell growth arrest by controlling biogenesis of 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). The role of RRM2 in EOC remains poorly understood. Here we show that RRM2 is expressed at higher levels in EOCs compared with either normal ovarian surface epithelium (P<0.001) or fallopian tube epithelium (P<0.001). RRM2 expression significantly correlates with the expression of Ki67, a marker of cell proliferation (P<0.001). Moreover, RRM2 expression positively correlates with tumor grade and stage, and high RRM2 expression independently predicts a shorter overall survival in EOC patients (P<0.001). To delineate the functional role of RRM2 in EOC, we knocked down RRM2 expression in a panel of EOC cell lines. Knockdown of RRM2 expression inhibits the growth of human EOC cells. Mechanistically, RRM2 knockdown triggers cellular senescence in these cells. Notably, this correlates with the induction of the DNA damage response, a known mediator of cellular senescence. These data suggest that targeting RRM2 in EOCs by suppressing its activity is a novel pro-senescence therapeutic strategy that has the potential to improve survival of EOC patients.
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