ArticleOncogene2017
Repression of caspase-3 and RNA-binding protein HuR cleavage by cyclooxygenase-2 promotes drug resistance in oral squamous cell carcinoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- ELAVL1 Promotes Proliferation and Inhibits Apoptosis of the Marek's Disease Virus (MDV)-Transformed Cell Line MSB1 via the COX-2/PGE2 Pathway.Animals : an open access journal from MDPI · 2026Article
- CDC5L binds to ELAVL1 to inhibit pyroptosis in hepatocellular carcinoma through the Caspase 3/GSDME signaling pathway.International journal of molecular medicine · 2025Article
- Potential application of nanodelivery systems targeting ELAVL1 in prostate cancer treatment.Frontiers in oncology · 2025Review
- An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR.Cell death discovery · 2024Article
- RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.Oral oncology reports · 2024Article
- RNA binding proteins in cancer chemotherapeutic drug resistance.Frontiers in cell and developmental biology · 2024Review
- Feline SCCs of the Head and Neck Display Partial Epithelial-Mesenchymal Transition and Harbor Stem Cell-like Cancer Cells.Pathogens (Basel, Switzerland) · 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
- HuR as a molecular target for cancer therapeutics and immune-related disorders.Advanced drug delivery reviews · 2022Review
- Article
- A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy.Journal of nanobiotechnology · 2021Article
- MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines.International journal of molecular sciences · 2021Article
- LncRNA HAND2-AS1 exerts anti-oncogenic effects on bladder cancer via restoration of RARB as a sponge of microRNA-146.Cancer cell international · 2021Article
- Cyclooxygenase-2 expression is associated with chemoresistance through cancer stemness property in hypopharyngeal carcinoma.Oncology letters · 2021Article
- Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review).Molecular medicine reports · 2021Article
- Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.Cancer research · 2021Article
- Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis.International journal of molecular sciences · 2020Review
- DeepCleave: a deep learning predictor for caspase and matrix metalloprotease substrates and cleavage sites.Bioinformatics (Oxford, England) · 2020Article
- Targeting exosome-associated human antigen R attenuates fibrosis and inflammation in diabetic heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- UBE2N Regulates Paclitaxel Sensitivity of Ovarian Cancer via Fos/P53 Axis.OncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
A well-studied RNA-binding protein Hu Antigen-R (HuR), controls post-transcriptional gene regulation and undergoes stress-activated caspase-3 dependent cleavage in cancer cells. The cleavage products of HuR are known to promote cell death; however, the underlying molecular mechanisms facilitating caspase-3 activation and HuR cleavage remains unknown. Here, we show that HuR cleavage associated with active caspase-3 in oral cancer cells treated with ionizing radiation and chemotherapeutic drug, paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of caspase-3 and HuR, which reduced the rate of cell death in paclitaxel resistant oral cancer cells. Specific inhibition of COX-2 by celecoxib, promoted apoptosis through activation of caspase-3 and cleavage of HuR in paclitaxel-resistant oral cancer cells, both in vitro and in vivo. In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA, promoted COX-2 protein expression and exhibited enhanced tumor growth in vivo in comparison with cells expressing a cleavable form of HuR. Finally, our ribonucleoprotein immunoprecipitation and sequencing (RIP-seq) analyses of HuR in oral cancer cells treated with ionizing radiation (IR), determined that HuR cleavage product-1 (HuR-CP1) bound and promoted the expression of mRNAs encoding proteins involved in apoptosis. Our results indicated that, cellular non-cleavable HuR controls COX-2 mRNA expression and enzymatic activity. In addition, overexpressed COX-2 protein repressed the cleavage of caspase-3 and HuR to promote drug resistance and tumor growth. Altogether, our observations support the use of the COX-2 inhibitor celecoxib, in combination with paclitaxel, for the management of paclitaxel resistant oral cancer cells.
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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.