TY - JOUR
T1 - Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer
AU - Wilson, Andrew J.
AU - Fadare, Oluwole
AU - Beeghly-Fadiel, Alicia
AU - Son, Deok Soo
AU - Liu, Qi
AU - Zhao, Shilin
AU - Saskowski, Jeanette
AU - Uddin, Md Jashim
AU - Daniel, Cristina
AU - Crews, Brenda
AU - Lehmann, Brian D.
AU - Pietenpol, Jennifer A.
AU - Crispens, Marta A.
AU - Marnett, Lawrence J.
AU - Khabele, Dineo
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Cell migration/invasion
KW - Cyclooxygenase-1
KW - High-grade serous ovarian cancer
KW - Pro-tumorigenic pathways
UR - http://www.scopus.com/inward/record.url?scp=84940737019&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3860
DO - 10.18632/oncotarget.3860
M3 - Article
C2 - 25972361
AN - SCOPUS:84940737019
SN - 1949-2553
VL - 6
SP - 21353
EP - 21368
JO - Oncotarget
JF - Oncotarget
IS - 25
ER -