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| Status |
Public on Feb 14, 2017 |
| Title |
Interaction between cyclooxygenase-2 and caspase-3 abolishes the cleavage of RNA-binding protein HuR and promotes drug resistance in oral squamous cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Here, we show that HuR cleavage is dependent on active caspase-3 in oral cancer cells treated with ionizing radiation and the chemotherapeutic drug paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of both caspase-3 and HuR, which in turn, reduced the rate of apoptosis in paclitaxel treated 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. In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA and promoted COX-2 expression, exhibiting enhanced tumor growth in vivo in comparison with the cleavable form of HuR. Finally, our RNP IP and RNA transcriptome analysis of HuR under IR revealed that the HuR cleavage product-1 (HuR-CP1) associates and promotes the expression of mRNAs encoding proteins involved in apoptosis.
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| Overall design |
4 samples: The GFP plasmid vectors containing full-length HuR, HuR-D226A, HuR-CP1 were expressed in oral cancer cells. GFP empty vector served as a control. HuR RNP IP was performed and RNA sequencing carried out.
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| Contributor(s) |
Hardiman G, Palanisamy V |
| Citation(s) |
27941877 |
| Submission date |
Mar 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gary Hardiman |
| E-mail(s) |
ghardimanwork@gmail.com
|
| Phone |
8437920771
|
| Organization name |
MUSC
|
| Street address |
135 Cannon Street, Suite 303 MSC835
|
| City |
Charleston |
| State/province |
SOUTH CAROLINA |
| ZIP/Postal code |
29425 |
| Country |
USA |
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| Platforms (1) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA315952 |
| SRA |
SRP072163 |
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