MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression

Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis of OSCC. However, the potential mechanisms have not been clarified yet. This study aimed to evaluate the role of miR-378 in the migration and invasion of OSCC in vitro and in vivo. According to our results, the migration and invasion abilities were increased in miR-378-overexpressing cells, while decreased in miR-378-3p/5p-silencing cells. In addition, overexpression of miR-378 suppressed the expressions and activities of MMP-9 and MMP-2. Epithelial-mesenchymal transition (EMT) was restrained by overexpression of miR-378 as evidenced by increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, the miR-378-3p/5p knockdown groups had the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed miR-378 overexpression-induced decrease in migration and invasion via upregulating MMP-9, MMP-2, and N-cadherin levels, while downregulating E-cadhrin level. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the metastasis nodule number was raised by miR-378 knockdown. Taken together, our study suggests that miR-378/KLK4 axis is involved in the mechanisms of the migration and invasion of OSCC cells. Targeting miR-378/KLK4 axis may be an effective measure for treating OSCC.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author