Overexpression of MicroRNA-138 Affects the Proliferation and Invasion of Urothelial Carcinoma Cells by Suppressing SOX9 Expression

Abstract

SRY-box transcription factor 9 (SOX9) is important for sexual differentiation, chondrogenic differentiation, and cell proliferation in cancer. It acts as a target molecule of microRNA (miR)-138 in various tumors and is associated with tumor development and growth. In this study, we analyzed the functions of miR-138 and SOX9 in urothelial carcinoma. SOX9 was highly expressed in invasive urothelial carcinoma tissues. miR-138 precursor transfection of T24 and UMUC2 cells significantly decreased SOX9 expression, indicating that SOX9 is a miR-138 target in urothelial carcinoma. Moreover, miR-138 precursor or SOX9 small interfering RNA (siRNA) transfection decreased the proliferation of urothelial carcinoma cell lines. To further confirm that miR-138–SOX9 signaling is involved in cell proliferation and invasion, urothelial carcinoma cells were transfected with the miR-138 precursor or SOX9 siRNA. This transfection reduced the proliferation and invasion of cells via the promotion of autophagy and apoptosis and G0/G1 cell cycle arrest. These results suggest that miR-138–SOX9 signaling modulates the growth and invasive potential of urothelial carcinoma cells.

Keywords

• urothelial carcinoma
• SOX9
• miR-138
• autophagy
• apoptosis