Background: Bladder cancer (BCa) is a common malignant disease with high recurrence and poor prognosis. Several circular RNAs (circRNAs) have been found to be associated with the malignant progression of bladder cancer (BCa). Here, the aim of this study was to investigate the expression, role and mechanism of circRAPGEF5 in BCa progression.
Methods: Quantitative real-time PCR (qRT-PCR) and immunoblotting were used to detect gene and protein expression levels. In vitro functional studies were performed using CCK-8, colony formation, wound healing and Transwell assays, respectively, and a mouse xenograft tumor model was established to perform in vivo experiments. Bioinformatic predictions as well as luciferase reporter assays and RNA pull-down assays were used to probe circRAPGEF5-mediated competitive endogenous RNA (ceRNA) network.
Results: CircRAPGEF5 was significantly overexpressed in BCa patients (p < 0.05), indicating a potential unsatisfactory prognosis. Functionally, knockdown of circRAPGEF5 inhibited the growth, migration and invasion of BCa cells in vitro (p < 0.05), as well as BCa growth in vivo (p < 0.05). Mechanistically, circRAPGEF5 acted as a sponge for miR-582-3p and targeted kinesin family member 3A (KIF3A). In addition, rescue experiments showed that inhibition of miR-582-3p or overexpression of KIF3A reversed the anticancer effects of circRAPGEF5 knockdown on BCa cells (p < 0.05).
Conclusion: Silencing circRAPGEF5 inhibits BCa proliferation, migration and invasion via the miR-582-3p/KIF3A axis, demonstrating a promising target for BCa-targeted therapy.
Keywords: Bladder cancer; Circular RNA; KIF3A; Tumorigenesis; miR-582-3p.
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