Lin Xu, Bin Shen, Tingting Chen, Pin Dong

The development of laryngeal squamous cell carcinoma (LSCC) is a multistep process involving multiple factors. MicroRNAs, a group of important negative regulators of gene expression, have also been confirmed to be involved in the LSCC pathogenesis. In the present study, we compared the expression of nine selected microRNAs in the LSCC tissues and adjacent nontumor tissues. We found that the expression of miR-203 was significantly reduced in the LSCC tissues. Predicted by using bioinformatics tools, we found that VEGFA and cyclooxygenase-2 (Cox-2) may be direct targets of miR-203. By subsequent determination through dual-luciferase assay and Western blot, we confirmed that miR-203 suppresses the expression of VEGFA and Cox-2 by directly targeting 3'-untranslated region. Meanwhile, by analyzing the relationship between miR-203 and VEGFA in clinical tissue samples, we found that a negative correlation existed in the expression of miR-203 and VEGFA (P=0.0096, r=-0.33). Similarly, the expression of miR-203 and Cox-2 also has a negative correlation (P=0.0019, r=-0.46). Subsequently, in vitro functional study indicated that miR-203 played as a tumor suppressor by repressing proliferation, migration, and invasion of Hep-2 cells. The overexpression of VEGFA partially rescued the effect of overexpressed miR-203. Overexpressed Cox-2 partially rescued the effect of miR-203 on Hep-2 cell proliferation but not on the cell migration and invasion capacity. These findings suggest that miR-203 plays as a tumor suppressor in LSCC, partially by regulating VEGFA and Cox-2, and may serve as a potential target for therapeutic intervention.