ArticleProceedings of the National Academy of Sciences of the United States of America2026
Differential roles of type I topoisomerases in regulating HPV pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Topoisomerase inhibitors in cervical cancer: mechanistic insights and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2026Review
- Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rewired DDR-TGF-β-β-catenin-PD-L1 axis accelerates progression and shapes therapy in human papillomavirus-driven cancer.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
High-risk human papillomaviruses (HPVs) activate the Ataxia Telangiectasia Mutated and Ataxia Telangiectasia and Rad3-Related pathways by inducing DNA breaks through the action of viral oncoproteins E6 and E7, which target factors such as topoisomerases. Type I topoisomerases cleave and religate a single strand of DNA, and little is known about how they regulate HPV pathogenesis. The levels of type I topoisomerases, TOP1α, TOP3α, and TOP3β, were all elevated in cells maintaining high-risk HPV genomes, as well as in squamous cell carcinomas. Only TOP1α and TOP3β, but not TOP3α, bound to HPV genomes and were critical for regulating viral gene transcription and replication with little effect on cell growth. Furthermore, the knockdown of TOP1α or TOP3β reduced levels of DNA breaks and differentially altered the expression of genes in key pathways. TOP1α knockdown reduced the expression of IL6 and activation of the procytokine signaling pathway. In contrast, TOP3β targeted EGR3, which regulates growth and differentiation. Finally, TOP1α and TOP3β differentially regulate the formation of R-loops, which are critical for viral replication. These findings demonstrate the differential roles of type I topoisomerases in HPV pathogenesis.
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Registered trials
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