Circ_0002099 is a novel molecular therapeutic target for bladder cancer.

Abstract

Bladder cancer (BLCA) acts as one of the most common malignant tumors in the urinary system without ideal therapy. We performed the present study to explore the role and mechanism of Circ_0002099 in BLCA progression. RNase R treatment assay and actinomycin D treatment assay were used to confirm the circular structure of Circ_0002099. Nuclear-cytoplasmic fractionation assay and fluorescence in situ hybridization (FISH) were used to indicatethe subcellular localization of Circ_0002099. The CCK-8 assay, colony formation assay, wound-healing assay, Transwell assay, and animal experiment were used to reveal the facilitative effect of Circ_0002099 on BLCA both in vitro and in vivo. Furthermore, bioinformatic analysis, western blot analysis, FISH,and dual-luciferase reporter assay were conducted to demonstrate the role of Circ_0002099 in BLCA progression. The results indicated that Circ_0002099 was significantly upregulated in BLCA and could enhance the progression of BLCA in vivo and in vitro. Furthermore, dual-luciferase reporter assay and FISHassay revealed that Circ_0002099 could regulate miR-217-5p/miR-103a-3p/Kirsten RAS (KRAS) axis in BLCA. In addition, rescue experiments confirmed that miR-217-5p/miR-103a-3p could rescue the facilitative effect of Circ_0002099 on BLCA progression. Moreover, FUS(FUSed in sarcoma)was identified to regulate the Circ_0002099-miR-217-5p/miR-103a-3p/KRAS axis in BLCA progression. The present study suggested that FUS-medicated Circ_0002099 could promote the epithelial-mesenchymal transitionprocess in BLCA progression via miR-217-5p/miR-103a-3p/KRAS axis-WNT/β-catenin axis. It could be a promising prognostic biomarker and therapeutic target for BLCA.