Abstract
ABSTRACTThe COX-2/PGE2 axis can play roles in mediating the progression of tumor. COX-2 induction was observed in oral cancer. In our previous study, we found Staphylococcus aureus, a pathogen prevalent in oral cancer, can activate the COX-2/PGE2 pathway in human oral keratinocyte (HOK) cells. Here, we investigated the proliferation of HOK cells affected by COX-2 induction and the role of COX-2 induction in the malignant transformation of HOK cells. We found S. aureus was able to facilitate HOK cell proliferation through upregulating COX-2 expression. With the induction of COX-2, expression of oral cancer-associated genes cyclin D1 was upregulated and p16 was downregulated. Transcriptome analysis showed that the “NF−kappa B signaling pathway” and “TNF signaling pathway” had the highest enrichment of differentially expressed genes (DEGs) with COX-2 over-expression. Seven upregulated genes (jun, tlr4, cxcl1, lif, cxcl3, tnfrsf1β, and il1β) in these two pathways were critical for the increased proliferation of HOK cells and might be associated with COX-2. Malignant transformation of cells was evaluated by soft agar colony formation assay and S. aureus infection promoted HOK cell colony formation. These results suggest the potential of S. aureus to induce the infection-associated malignant transformation of oral epitheliums through COX-2 activation.
Highlights
Y COX-2 induction and the role of COX-2 induction in the malignant transformation of human oral keratinocyte (HOK) cells
Using heat-inactivated S. aureus and supernatants from S. aureus cultures, we investigated whether the live cells or the secretory components of S. aureus were essential for the activation of the COX-2/PGE2 pathway in HOK cells
We evaluated PGE2 production by ELISA and found that HOK cells cocultured with live S. aureus and with heat-inactivated S. aureus produced PGE2 at a level of 502.16 pg/mL and 516.96 pg/mL, respectively, both of which were higher than the 383.12 pg/mL produced by untreated HOK cells
Summary
Y COX-2 induction and the role of COX-2 induction in the malignant transformation of HOK cells. With the induction of COX-2, expression of oral cancer-associated genes cyclin D1 was upregulated and p16 was downregulated. Malignant transformation of cells was evaluated by soft agar colony formation assay and S. aureus infection promoted HOK cell colony formation. These results suggest the potential of S. aureus to induce the infection-associated malignant transformation of oral epitheliums through COX-2 activation. We found that S. aureus can induce Cyclooxygenase-2 (COX-2) expression and PGE2 production in human oral keratinocyte (HOK) cells [19]. Considering the important role of COX-2 in oral cancers, it would be of great interest to study the potential for the malignant transformation of oral epithelial cells after the induction of COX-2 by S. aureus.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
