ArticleOncotarget2018
Inhibition of IRES-dependent translation of caspase-2 by HuR confers chemotherapeutic drug resistance in colon carcinoma cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Current Practice in Bicistronic IRES Reporter Use: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- The Cap-Independent Translation of Survivin 5'UTR and HIV-1 IRES Sequences Is Inhibited by Oxidative Stress Produced byBiomolecules · 2026Article
- 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
- Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages.iScience · 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
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
- Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis.Human cell · 2021Article
- A macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus.Nature communications · 2020Article
- Advantages of Using Paclitaxel in Combination with Oncolytic Adenovirus Utilizing RNA Destabilization Mechanism.Cancers · 2020Article
- The RNA-Binding Protein HuR in Digestive System Tumors.BioMed research international · 2020Review
- Article
- Human antigen R and drug resistance in tumors.Investigational new drugs · 2019Review
- Review
- IRES Trans-Acting Factors, Key Actors of the Stress Response.International journal of molecular sciences · 2019Review
- AU-rich element-binding proteins in colorectal cancer.World journal of gastrointestinal oncology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HuR plays an important role in tumor cell survival mainly through posttranscriptional upregulation of prominent anti-apoptotic genes. In addition, HuR can inhibit the translation of pro-apoptotic factors as we could previously report for caspase-2. Here, we investigated the mechanisms of caspase-2 suppression by HuR and its contribution to chemotherapeutic drug resistance of colon carcinoma cells. In accordance with the significant drug-induced increase in cytoplasmic HuR abundance, doxorubicin and paclitaxel increased the interaction of cytoplasmic HuR with the 5'untranslated region (5'UTR) of caspase-2 as shown by RNA pull down assay. Experiments with bicistronic reporter genes furthermore indicate the presence of an internal ribosome entry site (IRES) within the caspase-2-5'UTR. Luciferase activity was suppressed either by chemotherapeutic drugs or ectopic expression of HuR. IRES-driven luciferase activity was significantly increased upon siRNA-mediated knockdown of HuR implicating an inhibitory effect of HuR on caspase-2 translation which is further reinforced by chemotherapeutic drugs. Comparison of RNA-binding affinities of recombinant HuR to two fragments of the caspase-2-5'UTR by EMSA revealed a critical HuR-binding site residing between nucleotides 111 and 241 of caspase-2-5'UTR. Mapping of critical RNA binding domains within HuR revealed that a fusion of RNA recognition motif 2 (RRM2) plus the hinge region confers a full caspase-2-5'UTR-binding. Functionally, knockdown of HuR significantly increased the sensitivity of colon cancer cells to drug-induced apoptosis. Importantly, the apoptosis sensitizing effects by HuR knockdown were rescued after silencing of caspase-2. The negative caspase-2 regulation by HuR offers a novel therapeutic target for sensitizing colon carcinoma cells to drug-induced apoptosis.
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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.