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

Author:

Nitta Yuji1,Fujii Tomomi12,Uchiyama Tomoko1,Sugimoto Aya1,Nishikawa Takeshi13,Takeda Maiko1,Miyake Makito4ORCID,Shimada Keiji5,Fujimoto Kiyohide4ORCID

Affiliation:

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.

Funder

Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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