Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer.

Wilson AJ, Fadare O, Beeghly-Fadiel A, Son DS, Liu Q, Zhao S, Saskowski J, Uddin MJ, Daniel C, Crews B, Lehmann BD, Pietenpol JA, Crispens MA, Marnett LJ, Khabele D
Oncotarget. 2015 6 (25): 21353-68

PMID: 25972361 · PMCID: PMC4673270 · DOI:10.18632/oncotarget.3860

Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.

MeSH Terms (19)

Carcinoma, Ovarian Epithelial Cell Line, Tumor Cell Movement Cell Proliferation Computational Biology Cyclooxygenase 1 Female Gene Expression Profiling Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genome, Human Humans Immunohistochemistry Neoplasm Invasiveness Neoplasms, Glandular and Epithelial Neovascularization, Pathologic Oligonucleotide Array Sequence Analysis Ovarian Neoplasms Signal Transduction

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