Rui M Gil DA Costa1,2,3, Rita Araújo4,5, Joana M O Santos4,5, Mara Fernandes4,6,7, Tiago Neto4,3,5, Hugo Sousa4,8, Joana Ribeiro4,8, Margarida M S M Bastos2, Paula A Oliveira3,9, Diogo Carmo10, Fátima Casaca10, Sandra Silva10, Carlos Lopes11, Rui Medeiros4,5,7,8,12. 1. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Porto, Portugal rmcosta@fe.up.pt. 2. LEPABE, Faculty of Engineering, University of Porto, Porto, Portugal. 3. Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tras-os-Montes and Alto Douro (UTAD), Vila Real, Portugal. 4. Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Porto, Portugal. 5. ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal. 6. FMUP, Faculty of Medicine, University of Porto, Porto, Portugal. 7. LPCC, Research Department Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro-Nucleo Regional do Norte), Porto, Portugal. 8. Virology Service, Portuguese Institute of Oncology of Porto, Porto, Portugal. 9. Veterinary Sciences Department, University of Tras-os-Montes and Alto Douro (UTAD), Vila Real, Portugal. 10. Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal. 11. Experimental Pathology and Therapeutics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO-Porto), Porto, Portugal. 12. CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal.
Abstract
BACKGROUND/AIM: Human papillomavirus type 16 (HPV16) induces various types of cancer in several locations. Microenvironmental microRNAs (miRNAs) such as miRNA-146a and miRNA-150 regulate cancer-associated inflammation and are involved in HPV-induced carcinogenesis. We studied the effects of celecoxib on the expression of these two miRNAs in HPV16-induced lesions. MATERIALS AND METHODS: Female transgenic (HPV16+/-) and wild-type (HPV16-/-) mice were administered 75 mg/kg/day celecoxib orally (treatment groups) or placebo (control groups) for four weeks. Skin samples were classified histologically, or used for miRNA analysis by quantitative real-time PCR. RESULTS: HPV16+/- mice showed higher miRNA-146a and miRNA-150 expression levels compared to wild-type animals. Celecoxib further increased miRNA-150 (p<0.05) and miRNA-146a levels in treated animals. Celecoxib-treated HPV16+/- animals also showed reduced incidence of epidermal dysplasia and reduced inflammation, compared to untreated mice. CONCLUSION: In this model, celecoxib may be able to regulate tumour-associated inflammation, through mechanisms involving the regulation of miRNA-146a and miRNA-150. Copyright
BACKGROUND/AIM: Human papillomavirus type 16 (HPV16) induces various types of cancer in several locations. Microenvironmental microRNAs (miRNAs) such as miRNA-146a and miRNA-150 regulate cancer-associated inflammation and are involved in HPV-induced carcinogenesis. We studied the effects of celecoxib on the expression of these two miRNAs in HPV16-induced lesions. MATERIALS AND METHODS: Female transgenic (HPV16+/-) and wild-type (HPV16-/-) mice were administered 75 mg/kg/day celecoxib orally (treatment groups) or placebo (control groups) for four weeks. Skin samples were classified histologically, or used for miRNA analysis by quantitative real-time PCR. RESULTS:HPV16+/- mice showed higher miRNA-146a and miRNA-150 expression levels compared to wild-type animals. Celecoxib further increased miRNA-150 (p<0.05) and miRNA-146a levels in treated animals. Celecoxib-treated HPV16+/- animals also showed reduced incidence of epidermal dysplasia and reduced inflammation, compared to untreated mice. CONCLUSION: In this model, celecoxib may be able to regulate tumour-associated inflammation, through mechanisms involving the regulation of miRNA-146a and miRNA-150. Copyright