<scp>MicroRNA</scp> ‐mediated extracellular matrix remodeling in squamous cell carcinoma of the oral cavity
Gilberto Mendes Menderico, Thérèse Rachell Theodoro, Fátima Solange Pasini, Marina de Menezes Ishikawa, Nayara Santos, Evandro Sobroza de Mello, Maria Aparecida da Silva Pinhal, Raquel Ajub Moysés, Marco Aurélio Vamondes Kulcsar, Rogério Aparecido Dedivitis, Cláudio Roberto Cernea, Luiz Paulo Kowalski, Leandro Luongo Matos
Abstract
BACKGROUND: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa. METHODS: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes. RESULTS: High expression of miR-21-5p (p < 0.001) and miR-106-5p (p < 0.001) and low expression of miR-320a (p = 0.001) and miR-222-3p (p = 0.001) were predictors of malignancy. Individually, miR-21-5p exhibited the best statistical performance (area under the curve = 0.972; 95% confidence interval: 0.911-1.000) in the differentiation between tumor tissue and healthy mucosa. Moreover, tumor sample showed increased expression of MMP-2, MMP-9, α-laminin, and β-laminin in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane. CONCLUSION: The present study demonstrates the biological effects of microRNAs on the carcinogenesis of OSCC as well as the intense modification of the tumor microenvironment.