Background: It has been demonstrated that for oral cavity squamous cell carcinoma (SCC) as tumor thickness increases, there are lower rates of survival. Several molecular factors have been studied to determine this invasive behavior, including microRNAs, that play a role in the tumor microenvironment.
Methods: The aim of this study is evaluate the role of extracellular matrix remodeling, as well as the involvement of microRNAs, in the process of oral cavity SCC carcinogenesis. This was a retrospective study with patients operated on for SCC of the oral cavity, in addition to a group of oral mucosa samples from paired patients. RNA extraction was performed, followed by complementary DNA amplification of microRNAs related to adhesion, migration, cell proliferation, apoptosis, and constituents of the extracellular matrix. We also performed immunohistochemical reactions for markers involved in the same biological processes.
Results: High expression of miR-21-5p and miR-106-5p and low expression of miR-320a and miR-222-3p were predictors of malignancies and mir21-5p, individually, showed the best differentiation between the groups (AUC = 0.972). Regarding the immunohistochemical markers, there was greater expression of p53, EGFR, metalloproteinase-2 (MMP-2), laminin beta, Ki-67 and CD34 in the tumor cells than in the healthy mucosa. Furthermore, increased expression of MMP-2, metalloproteinase-9 (MMP-9), laminin alpha and laminin beta in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane were observed.
Conclusions: These results demonstrate the biological effects of microRNAs on the carcinogenesis of SCC of the oral cavity as well as the intense modification of the tumor microenvironment.