Regulation of miRNA-146a and miRNA-150 Levels by celecoxib in premalignant lesions of K14-HPV16 mice

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 celecoxi...

Full description

Bibliographic Details
Main Author: Gil da Costa, R. M. (author)
Other Authors: Araujo, R (author), Santos, JMO (author), Fernandes, M (author), Neto, T (author), Sousa, H (author), Ribeiro, J (author), Margarida Bastos (author), Oliveira, PA (author), Carmo, D (author), Casaca, F (author), Silva, S (author), Lopes, C (author), Medeiros, R (author)
Format: article
Language:eng
Published: 2017
Online Access:https://repositorio-aberto.up.pt/handle/10216/115858
Country:Portugal
Oai:oai:repositorio-aberto.up.pt:10216/115858
Description
Summary: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.