Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression

Abstract

Aberrantly expressed microRNAs (miRNAs) are involved in oral tumorigenesis since they can alter the expression of proteins involved in cancer progression. It remains unclear whether miRNA-221 influences the resistance of human oral squamous cell carcinoma cells to Adriamycin. We therefore investigated the role of miR-221 in the sensitivity of oral squamous cell carcinoma cells to chemotherapy. Tca8113 and UM2 cells were treated with different concentrations of Adriamycin. Quantitative real-time PCR (qRT-PCR) revealed miR-221 upregulation after Adriamycin treatment of Tca8113 and UM2 cells. By using miR-221 inhibitor mimics, we found that depleting cells of miR-221 increases the sensitivity of the cells to Adriamycin. The expression of tissue inhibitor of metalloproteinase-3 (TIMP3), a target of miR-221, was decreased in cells treated with Adriamycin. TIMP3 depletion reversed the effect of a miR-221 inhibitor mimics on cell survival rates and apoptosis. Together, these results reveal that silencing of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression.

Keywords: Adriamycin; Oral squamous cell carcinoma; TIMP3; miR-221.