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Cancer Sci. 2018 Nov 2. doi: 10.1111/cas.13857. [Epub ahead of print]

Silencing circular RNA UVRAG inhibits bladder cancer growth and metastasis by targeting the microRNA-223/fibroblast growth factor receptor 2 axis.

Yang C1,2, Wu S1,2, Wu X1,2, Zhou X3, Jin S4, Jiang H1,2.

Author information

1
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
2
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
3
Department of Urology, The Fifth People's Hospital of Shanghai, Shanghai, China.
4
Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Circular RNA UVRAG (circUVRAG), a type of non-coding RNA, is derived and cyclized by part of the exon from the UVRAG gene. However, the role of circUVRAG in bladder cancer (BLCA) has not been reported. The purpose of the present study was therefore to characterize the role of circUVRAG in BLCA. Bioinformatics analysis showed interactive relationships among circUVRAG, microRNA-223 (miR-223), and fibroblast growth factor receptor 2 (FGFR2). Quantitative real-time PCR was used to detect the expression of circUVRAG in BLCA cell lines. UM-UC-3 cells were stably transfected with siRNA against circUVRAG, and cell proliferation and migration ability were tested using the CCK8 assay, clone formation, and Transwell assays in vitro. Tumor xenograft formation and metastasis were determined using nude mice. Fluorescence in situ hybridization was used to confirm the subcellular localization of circUVRAG, and the luciferase reporter assay was used to confirm the relationships among circUVRAG, miR-223, and FGFR2. Results showed that circUVRAG was upregulated in BLCA cell lines. Downregulation of circUVRAG expression suppressed proliferation and metastasis both in vitro and in vivo. Downregulation of circUVRAG suppressed FGFR2 expression by "sponging" miR-223, which was confirmed by rescue experiments and luciferase reporter assay. Overall, the results showed that downregulation of circUVRAG suppressed the aggressive biological phenotype of BLCA. Taken together, silencing circular RNA UVRAG inhibited bladder cancer growth and metastasis by targeting the miR-223/FGFR2 axis, which may provide a potential biomarker and therapeutic target for the management of BLCA.

KEYWORDS:

FGFR2; bladder cancer; circular RNA UVRAG; metastasis; miR-223

PMID:
30387298
DOI:
10.1111/cas.13857
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