Transcriptomics,Genomics

Dataset Information

144

Interaction between cyclooxygenase-2 and caspase-3 abolishes the cleavage of RNA-binding protein HuR and promotes drug resistance in oral squamous cell carcinoma


ABSTRACT: 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. 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.

INSTRUMENT(S): Illumina HiScanSQ (Homo sapiens)

SUBMITTER: Gary Hardiman  

PROVIDER: GSE79477 | GEO | 2017-02-14

SECONDARY ACCESSION(S): PRJNA315952

REPOSITORIES: GEO

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Publications

Repression of caspase-3 and RNA-binding protein HuR cleavage by cyclooxygenase-2 promotes drug resistance in oral squamous cell carcinoma.

Janakiraman H H   House R P RP   Talwar S S   Courtney S M SM   Hazard E S ES   Hardiman G G   Mehrotra S S   Howe P H PH   Gangaraju V V   Palanisamy V V  

Oncogene 20161212 22


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, pa  ...[more]

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