ArticleCell & bioscience2023
Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Reprogramming the Tumor Oncobiosphere: Bioactive Nanohybrid Materials for Reversing Therapeutic Pseudo-Resistance.ACS omega · 2026Review
- RNA‑binding proteins as epithelial transcriptome orchestrators in gastric cancer: Immune‑metabolic crosstalk and therapeutic vulnerability (Review).International journal of molecular medicine · 2026Review
- Niclosamide attenuates skin cancer progression through suppression of key oncogenic pathways: integrated in vivo and in-silico mechanistic insights.BMC cancer · 2026Article
- High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma.Oncology letters · 2026Article
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- Functional interplay between TTP/ZFP36 and HuR/ELAVL1 in cancer: a post-transcriptional regulatory network.Frontiers in oncology · 2026Review
- Advancements in research on the role of the key glycolytic enzyme hexokinase 2 in the regulation of tumor immune evasion (Review).Oncology letters · 2025Review
- Targeting the HuR/E2F7 axis synergizes with bortezomib against multiple myeloma.Acta pharmacologica Sinica · 2025Article
- HAPIR: a refined Hallmark gene set-based machine learning approach for predicting immunotherapy response in cancer patients.NPJ precision oncology · 2025Article
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Glycoscience in Advancing PD-1/PD-L1-Axis-Targeted Tumor Immunotherapy.International journal of molecular sciences · 2025Review
- RNA-binding protein HuR regulates the transition of septic AKI to CKD by modulating CD147.Clinical science (London, England : 1979) · 2025Article
- Immune evasion and resistance in breast cancer.American journal of cancer research · 2025Review
- The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.Cancer heterogeneity and plasticity · 2025Article
- Post-transcriptional regulation by HuR in colorectal cancer: impacts on tumor progression and therapeutic strategies.Frontiers in immunology · 2025Review
- Navigating a complex dance: the interplay between RNA-binding proteins and T cells in oral epithelial plasticity.Immunometabolism (Cobham, Surrey) · 2025Review
- 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
- N-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment.Journal of translational medicine · 2024Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundImmune checkpoint blockade (ICB) represents a revolutionary advance in cancer treatment but remains limited success in triple-negative breast cancer (TNBC). Here we aim to explore the mechanism of RNA-binding protein (RBP) HuR in cancer immune evasion by post-transcriptionally regulating PD-L1 and evaluate the potential of HuR inhibition to improve immune response.
methodsThe binding between HuR and PD-L1 mRNA was determined by ribonucleoprotein immunoprecipitation and RNA pull-down assays. The HuR knockout clones were established by CRISPR/Cas9 technology. The protein levels were assessed by Western blot, immunohistochemistry, and immunocytochemistry. The function and molecular mechanism of HuR-PD-L1 were determined by in vitro T cell activation and killing assay and in vivo efficacy assay.
resultsWe found that HuR directly bound to and stabilized PD-L1 mRNA. Knocking out HuR reduced PD-L1 levels and promoted T cell activation. We discovered that niclosamide reduced PD-L1 by inhibiting HuR cytoplasmic translocation, and diminished glycosylation of PD-L1. Niclosamide enhanced T cell-mediated killing of cancer cells and significantly improved the efficacy of anti-PD-1 immunotherapy in two syngeneic animal tumor models.
conclusionWe identified HuR as a novel posttranscriptional regulator of PD-L1, which plays an important role in tumor immune evasion. Niclosamide might be a promising repurposed drug to improve the patient response to immunotherapy by targeting HuR-PD-L1 axis. Our study demonstrates a novel strategy for targeting HuR/PD-L1 and provides the first proof-of-principle for repurposing niclosamide as a HuR inhibitor to overcome cancer immune evasion and improve response to ICB immunotherapy.
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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.