Circular RNAs (circRNAs) are broad and diverse endogenous non-coding RNAs. Emerging evidence has revealed that circRNAs play pivotal roles in cancers, regulating the gene expression by acting as a microRNA (miRNA) sponge. However, the biological functions of circRNAs in bladder cancer (BCa) remain largely unknown. In this study, we identified an altered circRNA, termed circFUT8, by screening RNA sequencing data generated from three BCa tissues and matched adjacent normal bladder tissues. Quantitative real-time PCR analysis demonstrated that circFUT8 was downregulated in BCa tissues and correlated with patients’ prognosis, histological grade, and lymph node (LN) metastasis. Functionally, gain- and loss-of-function assays indicated that circFUT8 inhibited the migration and invasion of BCa cell lines in vitro and LN metastasis in vivo. Mechanistically, circFUT8 directly bound to miR-570-3p and partially abrogated its oncogenic role, and miR-570-3p could suppress the expression of tumor suppressor gene Krüpple-like factor 10 (KLF10) by binding its 3′ untranslated region (3′ UTR). Moreover, we found that circFUT8 promoted the expression of KLF10 by competitively sponging miR-570-3p. In conclusion, circFUT8 functions as a tumor suppressor in BCa cells by targeting the miR-570-3p/KLF10 axis and may serve as a potential biomarker and therapeutic target for the management of BCa patients with LN metastasis.

环状 RNA (circRNA) 是广泛且多样化的内源非编码 RNA。新的证据表明，circRNA 在癌症中发挥着关键作用，通过充当 microRNA (miRNA) 海绵来调节基因表达。然而，circRNA 在膀胱癌 (BCa) 中的生物学功能仍然很大程度上未知。在这项研究中，我们通过筛选从三个 BCa 组织和匹配的邻近正常膀胱组织生成的 RNA 测序数据，鉴定了一种改变的 circRNA，称为 circFUT8。实时定量PCR分析表明，circFUT8在BCa组织中表达下调，并与患者的预后、组织学分级和淋巴结（LN）转移相关。在功能上，功能获得和功能丧失测定表明，circFUT8 抑制体外BCa 细胞系的迁移和侵袭以及体内LN 转移。从机制上讲，circFUT8直接与miR-570-3p结合并部分消除其致癌作用，并且miR-570-3p可以通过结合其3′非翻译区（3′）来抑制肿瘤抑制基因Krüpple样因子10（KLF10）的表达UTR）。此外，我们发现circFUT8通过竞争性海绵miR-570-3p来促进KLF10的表达。总之，circFUT8 通过靶向 miR-570-3p/KLF10 轴在 BCa 细胞中发挥肿瘤抑制因子的作用，并可能作为治疗 LN 转移的 BCa 患者的潜在生物标志物和治疗靶点。