ArticleJournal of Cancer2019
HPV 16 E6/E7 up-regulate the expression of both HIF-1α and GLUT1 by inhibition of RRAD and activation of NF-κB in lung cancer cells.
Article in Journal of Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- The risk for subsequent primary lung cancer after cervical carcinoma: A quantitative analysis based on 864,627 cases.PloS one · 2024Pooled it
- Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2021Pooled it
- Gene Expression Analysis of Human Papillomavirus-Associated Colorectal Carcinoma.BioMed research international · 2020Trial
- LKB1 attenuates the transport activity of GLUT1 by regulating the alternative splicing of PKM1/PKM2 in cervical cancer.Journal of gynecologic oncology · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Chronic viral infections and their role in shaping the tumor immune microenvironment.Frontiers in immunology · 2026Review
- LKB1 promotes lung adenocarcinoma cell senescence by suppressing the O-GlcNAc glycosylation-mediated activation of telomerase.Frontiers in pharmacology · 2026Article
- Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.Journal of Cancer · 2026Review
- Inhibition of p16 and NF-κB Oncogenic Activity in Human Papillomavirus-Infected Cervical Cancer Cells: A New Role for Activating Transcription Factor-3.The Yale journal of biology and medicine · 2025Article
- Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis.Current issues in molecular biology · 2024Article
- HPV E6/E7: insights into their regulatory role and mechanism in signaling pathways in HPV-associated tumor.Cancer gene therapy · 2024Review
- Viral infection, APOBEC3 dysregulation, and cancer.Frontiers in genetics · 2024Review
- Human papillomavirus 16 E6 promotes angiogenesis of lung cancer via SNHG1.Cell biochemistry and biophysics · 2023Article
- Friend or Foe: Regulation, Downstream Effectors of RRAD in Cancer.Biomolecules · 2023Review
- miR-143-5p suppresses breast cancer progression by targeting the HIF-1α-related GLUT1 pathway.Oncology letters · 2022Article
- β-Boswellic Acid Suppresses Breast Precancerous LesionsFrontiers in oncology · 2022Article
- Long Non-coding RNA ENST00000453774.1 Confers an Inhibitory Effect on Renal Fibrosis by Inhibiting miR-324-3p to Promote NRG1 Expression.Frontiers in cell and developmental biology · 2021Article
- TRIP6 regulates the proliferation, migration, invasion and apoptosis of osteosarcoma cells by activating the NF-κB signaling pathway.Experimental and therapeutic medicine · 2020Article
- HPV 16 E6/E7 Promote the Glucose Uptake of GLUT1 in Lung Cancer Through Downregulation of TXNIP Due to Inhibition of PTEN Phosphorylation.Frontiers in oncology · 2020Article
- Possible Oncogenic Viruses Associated with Lung Cancer.OncoTargets and therapy · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. In our previous studies, we found that HPV16 E6/E7 up-regulated HIF-1α at protein level and further up-regulated GLUT1 at both protein and mRNA levels in well-established lung cancer cell lines. In one of our further mechanism study, the results demonstrated that HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-LKB1-HIF-1α-GLUT1 axis. However, there are multiple pathways involved in HPV16 E6/E7 regulation of HIF-1α expression. In current study, using double directional genetic manipulation in well-established lung cancer cell lines, we showed that both E6 and E7 down-regulated the expression of RRAD at both protein and mRNA levels. Like LKB1, RRAD is one of the cancer suppressor genes. The loss of RRAD further activated NF-κB by promoted cytoplasmic p65 translocated to nucleus, and up-regulated the expression level of the p-p65 in nucleus. Furthermore, p-p65 up regulated HIF-1α and GLUT1 at both protein and mRNA levels. Thus, we proposed HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-RRAD-p65- HIF-1α- GLUT1 axis. In conclusion, we demonstrated for the first time that E6 and E7 promoted the expression of HIF-1α and GLUT1 by relieving the inhibitory effect of RRAD which resulted in the activation of NF-κB by promoting cytoplasmic p65 translocated to nucleus, and up-regulated the expression of the p-p65 in nucleus in lung cancer cells. Our findings provided new evidence to support the critical role of RRAD in the pathogenesis of HPV-related lung cancer, and suggested novel therapeutic targets.
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