ArticleCancer research2014
HuR posttranscriptionally regulates WEE1: implications for the DNA damage response in pancreatic cancer cells.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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Who cites it
70 citing papers in PubMed, 105 citations in OpenAlex.
- Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer: A Post-hoc Analysis From the International Phase III ESPAC-3 Clinical Trial.Annals of surgery · 2018Trial
- P2X7R deficiency alleviates cardiac senescence by enhancing mitophagy via the HuR/TRIM26/NR4A1 axis.Clinical and translational medicine · 2026Article
- Oxaliplatin resistance in pancreatic ductal adenocarcinoma is non‑significantly mediated by diminished drug uptake but is highly linked to a poor apoptotic response to the cytotoxic threat.Oncology reports · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Expression and interaction of RNA binding protein HuR with multidrug transporters (P-GP, MRP1, and ABCG2) in chemoresistant breast and colorectal cancer cells.Journal, genetic engineering & biotechnology · 2025Article
- LINC00654 promotes ovarian cancer progression by facilitating nuclear export of HuR and stabilizing oncogenic mRNAs.Oncogene · 2025Article
- Long Non-Coding RNAs and RNA-Binding Proteins in Pancreatic Cancer Development and Progression.Cancers · 2025Review
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Tackling the HuRdle of radioresistance: a radiation perspective on the RNA-binding protein HuR.Translational cancer research · 2023Article
- Toxic Effects of Penetrating Cations.Membranes · 2023Review
- Functional inhibition of the RNA-binding protein HuR sensitizes triple-negative breast cancer to chemotherapy.Molecular oncology · 2023Article
- Targeting AHR Increases Pancreatic Cancer Cell Sensitivity to Gemcitabine through the ELAVL1-DCK Pathway.International journal of molecular sciences · 2023Article
- 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
- Increased glucose availability sensitizes pancreatic cancer to chemotherapy.Nature communications · 2023Article
- Deletion of the mRNA stability factorNAR cancer · 2023Article
- The Landscape and Therapeutic Targeting ofCurrent issues in molecular biology · 2023Review
- Small Molecules Targeting the RNA-Binding Protein HuR Inhibit Tumor Growth in Xenografts.Journal of medicinal chemistry · 2023Article
- Strategies for the Management of Patients with Pancreatic Cancer with PARP Inhibitors.Cancer treatment and research · 2023Article
- Wee1 promotes cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1.Cell communication and signaling : CCS · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
HuR (ELAV1), an RNA-binding protein abundant in cancer cells, primarily resides in the nucleus, but under specific stress (e.g., gemcitabine), HuR translocates to the cytoplasm in which it tightly modulates the expression of mRNA survival cargo. Here, we demonstrate for the first time that stressing pancreatic ductal adenocarcinoma (PDA) cells by treatment with DNA-damaging anticancer agents (mitomycin C, oxaliplatin, cisplatin, carboplatin, and a PARP inhibitor) results in HuR's translocation from the nucleus to the cytoplasm. Importantly, silencing HuR in PDA cells sensitized the cells to these agents, whereas overexpressing HuR caused resistance. HuR's role in the efficacy of DNA-damaging agents in PDA cells was, in part, attributed to the acute upregulation of WEE1 by HuR. WEE1, a mitotic inhibitor kinase, regulates the DNA damage repair pathway, and therapeutic inhibition of WEE1 in combination with chemotherapy is currently in early phase trials for the treatment of cancer. We validate WEE1 as a HuR target in vitro and in vivo by demonstrating (i) direct binding of HuR to WEE1's mRNA (a discrete 56-bp region residing in the 3' untranslated region) and (ii) HuR siRNA silencing and overexpression directly affects the protein levels of WEE1, especially after DNA damage. HuR's positive regulation of WEE1 increases γ-H2AX levels, induces Cdk1 phosphorylation, and promotes cell-cycle arrest at the G2-M transition. We describe a novel mechanism that PDA cells use to protect against DNA damage in which HuR posttranscriptionally regulates the expression and downstream function of WEE1 upon exposure to DNA-damaging agents.
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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.