ArticleCancer research2021
Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 32 citations in OpenAlex.
- Myeloid-specific tristetraprolin mitigates postsurgical incisional pain by suppressing proinflammatory responses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Myeloid-specific Tristetraprolin mitigates postsurgical incisional pain by suppressing proinflammatory responses.Research square · 2025Article
- The Roles of RNA-Binding Proteins in Vasculogenic Mimicry Regulation in Glioblastoma.International journal of molecular sciences · 2025Review
- Review
- Inhibition of the RNA Regulator HuR Mitigates Spinal Cord Injury by Potently Suppressing Post-Injury Neuroinflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Post-transcriptional regulation by HuR in colorectal cancer: impacts on tumor progression and therapeutic strategies.Frontiers in immunology · 2025Review
- Pilot Screening of TREM1 Inhibitors in Cell-Based Reporter Assays Reflecting TREM1/DAP12 Receptor Assembly and Functionality.ACS chemical neuroscience · 2025Article
- An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR.Cell death discovery · 2024Article
- Long Non-Coding RNA B3GALT5-AS1 Suppresses Keloid Progression by Regulating the β-Trcp1-Mediated Ubiquitination of HuR.Clinical, cosmetic and investigational dermatology · 2024Article
- Low expression of ZFP36L1 in osteosarcoma promotes lung metastasis by inhibiting the SDC4-TGF-β signaling feedback loop.Oncogene · 2024Article
- A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation.Nature communications · 2023Article
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- 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
- The IL13α 2R paves the way for anti-glioma nanotherapy.Genes & diseases · 2023Review
- Article
- Inhibition of the RNA Regulator HuR by SRI-42127 Attenuates Neuropathic Pain After Nerve Injury Through Suppression of Neuroinflammatory Responses.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- The RNA-binding protein HuR in human cancer: A friend or foe?Advanced drug delivery reviews · 2022Review
- The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.Advanced drug delivery reviews · 2022Review
- Drug delivery approaches for HuR-targeted therapy for lung cancer.Advanced drug delivery reviews · 2022Review
- Research progress on RNA-binding proteins in breast cancer.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The development of novel therapeutics that exploit alterations in the activation state of key cellular signaling pathways due to mutations in upstream regulators has generated the field of personalized medicine. These first-generation efforts have focused on actionable mutations identified by deep sequencing of large numbers of tumor samples. We propose that a second-generation opportunity exists by exploiting key downstream "nodes of control" that contribute to oncogenesis and are inappropriately activated due to loss of upstream regulation and microenvironmental influences. The RNA-binding protein HuR represents such a node. Because HuR functionality in cancer cells is dependent on HuR dimerization and its nuclear/cytoplasmic shuttling, we developed a new class of molecules targeting HuR protein dimerization. A structure-activity relationship algorithm enabled development of inhibitors of HuR multimer formation that were soluble, had micromolar activity, and penetrated the blood-brain barrier. These inhibitors were evaluated for activity validation and specificity in a robust cell-based assay of HuR dimerization. SRI-42127, a molecule that met these criteria, inhibited HuR multimer formation across primary patient-derived glioblastoma xenolines (PDGx), leading to arrest of proliferation, induction of apoptosis, and inhibition of colony formation. SRI-42127 had favorable attributes with central nervous system penetration and inhibited tumor growth in mouse models. RNA and protein analysis of SRI-42127-treated PDGx xenolines across glioblastoma molecular subtypes confirmed attenuation of targets upregulated by HuR. These results highlight how focusing on key attributes of HuR that contribute to cancer progression, namely cytoplasmic localization and multimerization, has led to the development of a novel, highly effective inhibitor. SIGNIFICANCE: These findings utilize a cell-based mechanism of action assay with a structure-activity relationship compound development pathway to discover inhibitors that target HuR dimerization, a mechanism required for cancer promotion.
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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.