ArticleMolecular therapy. Nucleic acids2022
DNA topoisomerase inhibition with the HIF inhibitor acriflavine promotes transcription of lncRNAs in endothelial cells.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Pathway-specific mechanisms, therapeutic applications, and toxicodynamic profile of acriflavine in cancer: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Argonaute 2 drives resistance to immune checkpoint inhibitors in immunorefractory non-small cell lung cancer.PLoS biology · 2026Article
- Long non-coding RNA LINC00607 epigenetically regulates endothelial TSPAN18 to promote hypoxia-induced thromboinflammation.The Journal of biological chemistry · 2026Article
- Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- LncRNAs Are Key Regulators of Transcription Factor-Mediated Endothelial Stress Responses.International journal of molecular sciences · 2024Review
- Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Is acriflavine an efficient co-drug in chemotherapy?RSC advances · 2023Article
- The endothelial-enriched lncRNA LINC00607 mediates angiogenic function.Basic research in cardiology · 2023Article
- Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.Journal of medicinal chemistry · 2022Review
- Perspectives of traditional Chinese medicine to patch up immune checkpoint blockers.Exploration of targeted anti-tumor therapy · 2022Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
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Abstract
The transcription factor hypoxia-inducible factor 1 (HIF1) is an important driver of cancer and is therefore an attractive drug target. Acriflavine (ACF) has been suggested to inhibit HIF1, but its mechanism of action is unknown. Here we investigated the interaction of ACF with DNA and long non-coding RNAs (lncRNAs) and its function in human endothelial cells. ACF promoted apoptosis and reduced proliferation, network formation, and angiogenic capacity. It also induced changes in gene expression, as determined by RNA sequencing (RNA-seq), which could not be attributed to specific inhibition of HIF1. A similar response was observed in murine lung endothelial cells. Although ACF increased and decreased a similar number of protein-coding genes, lncRNAs were preferentially upregulated under normoxic and hypoxic conditions. An assay for transposase accessibility with subsequent DNA sequencing (ATAC-seq) demonstrated that ACF induced strong changes in chromatin accessibility at lncRNA promoters. Immunofluorescence showed displacement of DNA:RNA hybrids. Such effects might be due to ACF-mediated topoisomerase inhibition, which was indeed the case, as reflected by DNA unwinding assays. Comparison with other acridine derivatives and topoisomerase inhibitors suggested that the specific function of ACF is an effect of acridinium-class compounds. This study demonstrates that ACF inhibits topoisomerases rather than HIF specifically and that it elicits a unique expression response of lncRNAs.
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