ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
RRM2 regulates Bcl-2 in head and neck and lung cancers: a potential target for cancer therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.Scientific reports · 2015Pooled it
- Subtype-specific clinical significance of RRM1 and RRM2 expression in non-small cell lung cancer: a TCGA-based analysis.Genes & genomics · 2026Article
- Resolvin D1 in the Lipopolysaccharide-Induced Inflammatory Microenvironment Mediates Resolution in Human Monocytic THP-1 Cells.Biomedicines · 2026Article
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- Molecular Effect of Tobacco on Genetic, Epigenetic, and Metabolic Pathways During Cancer Progression.Cureus · 2026Review
- Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer.Journal of translational medicine · 2025Article
- Chelerythrine Inhibits TGF-β-Induced Epithelial-Mesenchymal Transition in A549 Cells via RRM2.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting ribonucleotide reductase to enhance the antileukemic activity of gilteritinib against chemoresistantASPET discovery · 2025Article
- Deciphering the let-7c-5p/RRM2 axis in lung adenocarcinoma: expression, prognosis, and immune landscape implications.Frontiers in oncology · 2025Article
- Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cellsActa pharmaceutica Sinica. B · 2024Article
- The potential of ribonucleotide reductase M2 as a novel prognostic maker and therapeutic target to inhibit medulloblastoma proliferation, migration, and invasiveness.Pediatric discovery · 2024Article
- Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma.Current issues in molecular biology · 2024Article
- Multi-omics characterization and machine learning of lung adenocarcinoma molecular subtypes to guide precise chemotherapy and immunotherapy.Frontiers in immunology · 2024Article
- Higher concentration of P7C3 than required for neuroprotection suppresses renal cell carcinoma growth and metastasis.Journal of Cancer · 2024Article
- RRM2 as a novel prognostic and therapeutic target of NF1-associated MPNST.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Article
- Ribonucleotide reductase regulatory subunit M2 (RRM2) as a potential sero-diagnostic biomarker in non-small cell lung cancer.PloS one · 2023Article
- The Core-Targeted RRM2 Gene of Berberine Hydrochloride Promotes Breast Cancer Cell Migration and Invasion via the Epithelial-Mesenchymal Transition.Pharmaceuticals (Basel, Switzerland) · 2022Article
- MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2.Annals of translational medicine · 2022Article
- ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo.Cancers · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRibonucleotide reductase subunit M2 (RRM2) plays an active role in tumor progression. Recently, we reported that depletion of RRM2 by systemic delivery of a nanoparticle carrying RRM2-specific siRNA suppresses head and neck tumor growth. The aim of this study is to clarify the underlying mechanism by which RRM2 depletion inhibits tumor growth. EXPERIMENTAL
designsiRNA-mediated gene silencing was carried out to downregulate RRM2. Immunoblotting, reverse-transcriptase PCR, confocal microscopy, tissue fractionation, gene overexpression and knockdown were employed to analyze critical apoptosis signaling. Conventional immunohistochemistry and quantum dot-based immunofluorescence were applied to detect RRM2 and Bcl2 expression and localization in tissue samples from patients and mice.
resultsKnockdown of RRM2 led to apoptosis through the intrinsic pathway in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. We showed that Bcl-2 is a key determinant controlling apoptosis, both in vitro and in vivo, and that RRM2 depletion significantly reduces Bcl-2 protein expression. We observed that RRM2 regulates Bcl-2 protein stability, with RRM2 suppression leading to increased Bcl-2 degradation, and identified their colocalization in HNSCC and NSCLC cells. In a total of 50 specimens each from patients with HNSCC and NSCLC, we identified the colocalization of Bcl-2 and RRM2 and found a significant positive correlation between their expression in HNSCC (R = 0.98; P < 0.0001) and NSCLC (R = 0.92; P < 0.0001) tumor tissues.
conclusionsOur novel findings add to the knowledge of RRM2 in regulating expression of the antiapoptotic protein Bcl-2 and reveal a critical link between RRM2 and Bcl-2 in apoptosis signaling.
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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.