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

Yuji Nitta; Tomomi Fujii; Tomoko Uchiyama; Aya Sugimoto; Takeshi Nishikawa; Maiko Takeda; Makito Miyake; Keiji Shimada; Kiyohide Fujimoto

doi:10.3390/biomedicines11113064

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

Biomedicines. 2023 Nov 15;11(11):3064. doi: 10.3390/biomedicines11113064.

Authors

Yuji Nitta¹, Tomomi Fujii^{1

2}, Tomoko Uchiyama¹, Aya Sugimoto¹, Takeshi Nishikawa^{1

3}, Maiko Takeda¹, Makito Miyake⁴, Keiji Shimada⁵, Kiyohide Fujimoto⁴

Affiliations

¹ Department of Diagnostic Pathology, Nara Medical University School of Medicine, Nara 634-8521, Japan.
² Division of Fostering Required Medical Human Resources, Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka 565-0871, Japan.
³ Department of Central Clinical Laboratory, Nara Medical University Hospital, Nara 634-8521, Japan.
⁴ Department of Urology, Nara Medical University School of Medicine, Nara 634-8521, Japan.
⁵ Department of Diagnostic Pathology, Nara City Hospital, Nara 630-8305, Japan.

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: SOX9; apoptosis; autophagy; miR-138; urothelial carcinoma.

Grants and funding

This work was supported in part by a Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology (grant number 21K06906).