ArticleOncotarget2016
Inhibiting cytoplasmic accumulation of HuR synergizes genotoxic agents in urothelial carcinoma of the bladder.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 51 citations in OpenAlex.
- Pharmacologic disruption of HuR-RNA interactions prevents maladaptive tubular repair and AKI-to-CKD progression.American journal of physiology. Renal physiology · 2026Article
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels.BMC biology · 2025Article
- Post-transcriptional regulation by HuR in colorectal cancer: impacts on tumor progression and therapeutic strategies.Frontiers in immunology · 2025Review
- A Systematic Quantitative Approach to Rational Drug Design and the Discovery of Novel Human Antigen R (HuR) Inhibitors.Anti-cancer agents in medicinal chemistry · 2025Article
- A High-Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers.Cancer medicine · 2024Article
- Repurposing Niclosamide to Modulate Renal RNA-Binding Protein HuR for the Treatment of Diabetic Nephropathy in db/db Mice.International journal of molecular sciences · 2024Article
- Readers of RNA Modification in Cancer and Their Anticancer Inhibitors.Biomolecules · 2024Review
- HuR controls glutaminase RNA metabolism.Nature communications · 2024Article
- RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.Oral oncology reports · 2024Article
- The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer.Nature communications · 2023Article
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- Article
- Relationship between HuR and tumor drug resistance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- RNA-Binding Proteins in Bladder Cancer.Cancers · 2023Review
- Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.Biomedicines · 2022Review
- RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer.Advanced drug delivery reviews · 2022Review
- The RNA-binding protein HuR in human cancer: A friend or foe?Advanced drug delivery reviews · 2022Review
- Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia.Oxidative medicine and cellular longevity · 2022Article
- Drug delivery approaches for HuR-targeted therapy for lung cancer.Advanced drug delivery reviews · 2022Review
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
HuR, an RNA-binding protein, post-transcriptionally regulates nearly 4% of encoding proteins implicated in cell survival. Here we show that HuR is required for the efficacy of chemotherapies in urothelial carcinoma of the bladder. We identify pyrvinium pamoate, an FDA-approved anthelminthic drug, as a novel HuR inhibitor that dose-dependently inhibited cytoplasmic accumulation of HuR. Combining pyrvinium pamoate with chemotherapeutic agents (e.g. cisplatin, doxorubicin, vincristine and oxaliplatin) not only led to enhanced cytotoxicity in bladder cancer cells but also synergistically suppressed the growth of patient-derived bladder tumor xenografts in mice (P < 0.001). Mechanistically, pyrvinium pamoate promoted nuclear import of HuR by activating the AMP-activated kinase/importin α1 cascade and blocked HuR nucleo-cytoplasmic translocation by inhibiting the checkpoint kinase1/cyclin-dependent kinase 1 pathway. Notably, pyrvinium pamoate-additive treatment increased DNA double-strand breaks as indicated by elevated γH2AX expression, suggesting an involvement of DNA damage response. We further found that pyrvinium pamoate dramatically downregulated several key DNA repair genes in genotoxically-stressed cells, including DNA ligase IV and BRCA2, leading to unbearable genomic instability and cell death. Collectively, our findings are the first to characterize a clinical HuR inhibitor and provide a novel therapeutically tractable strategy by targeting cytoplasmic translocation of HuR for treatment of urothelial carcinoma of the bladder.
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Registered trials
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.