ArticleBritish journal of cancer2014
Increased expression of RRM2 by human papillomavirus E7 oncoprotein promotes angiogenesis in cervical cancer.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 117 citations in OpenAlex.
- Pathogenic Mechanisms in Cervical Cancer: Energy Metabolism, Hypoxia and Therapy.Life (Basel, Switzerland) · 2026Review
- Targeted therapies in primary vaginal cancer.Journal of cancer research and clinical oncology · 2025Article
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- Ribonucleotide-diphosphate reductase subunit M2 (RRM2) expression and colorectal cancer invasiveness: a potential prognostic biomarker.Molecular biology reports · 2025Article
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- MicroRNA Monitoring in Human Alveolar Macrophages from Patients with Smoking-Related Lung Diseases: A Preliminary Study.Biomedicines · 2024Article
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- For Better or Worse: Modulation of the Host DNA Damage Response by Human Papillomavirus.Annual review of virology · 2023Review
- Critical role for ribonucleoside-diphosphate reductase subunit M2 in ALV-J-induced activation of Wnt/β-catenin signaling via interaction with P27.Journal of virology · 2023Article
- Improvement of variables interpretability in kernel PCA.BMC bioinformatics · 2023Article
- Biochemistry-Not Oncogenes-May Demystify and Defeat Cancer.Oncology and therapy · 2023Review
- Regulatory Role of Ribonucleotide Reductase Subunit M2 in Hepatocyte Growth and Pathogenesis of Hepatitis C Virus.International journal of molecular sciences · 2023Review
- Functions and modulation of PKM2 activity by human papillomavirus E7 oncoprotein (Review).Oncology letters · 2023Review
- Associations of human papillomavirus genotypes and cervical vascular abnormality in a cohort of women underwent colposcopy, a retrospective study of 6716 patients.Frontiers in oncology · 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
- Identification and validation of a ferroptosis-related gene to predict survival outcomes and the immune microenvironment in lung adenocarcinoma.Cancer cell international · 2022Article
- A supervised machine learning approach identifies gene-regulating factor-mediated competing endogenous RNA networks in hormone-dependent cancers.Journal of cellular biochemistry · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe purpose of this study was to confirm that RRM2 as a novel target of HPVE7 involved in cervical cancer angiogenesis.
methodsGene expression was analysed by RT-qPCR, western blot and immunohistochemistry in cervical cancer tissue and cell lines. Luciferase reporter assay was used to determine the activities of various RRM2 promoters. Secreted VEGF was measured by ELISA. RRM2-mediated capillary tube formation induced by HPVE7 in cervical cancer cells were evaluated using human umbilical vein endothelial cells in vitro. ROS induced by RRM2 in cercal cancer cells was confirmed by flow cytometry. The growth of cervical cancer cell overexpression RRM2 was examined by nude mouse xenograft.
resultsRRM2 as a novel downstream target for HPVE7 was upregulated by it at the transcriptional level through the E7-pRb interaction and binding of E2F to the RRM2 promoter region. Immunohistochemical analysis showed that the level of RRM2 positively correlated with the HPVE7 level in human cervical cancer. Functionally, overexpression of RRM2 enhanced the expression of HIF-1α and VEGF via activation of the ERK1/2 signalling pathway in cervical cancer cells, and significantly associated with increased microvessel densities in cervical cancer tissues. In vitro, HPVE7 stimulated RRM2-dependent capillary tube formation by HUVECs, and RRM2-enhanced angiogenesis was VEGF dependent. RRM2-activated ERK1/2 pathway was mediated through production of ROS. In the xenograft mouse model, overexpression of RRM2 in cervical cancer cells enhanced tumour growth as well as microvessel densities.
conclusionHPVE7 induces upregulation of RRM2, which then promotes cervical carcinogenesis via ROS-ERK1/2-HIF-1α-VEGF-induced angiogenesis. Thus, the inhibition of RRM2 activity may be a novel therapeutic strategy for human cervical cancer.
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