Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Xinglong Road 29, Tianning, Changzhou, 213000, China.
Department of Urology Surgery, Changzhou Wujin People's Hospital, Wujin Hospital Affiliated Jiangsu University, The Wujin Clinical College of Xuzhou Medical University, Changzhou, China.
Biochem Genet. 2022 Dec;60(6):2327-2345. doi: 10.1007/s10528-022-10210-x. Epub 2022 Apr 1.
Bladder cancer (BCa) is the most common cancer in the urinary system with high recurrence rate and poor prognosis. Circular RNA (circRNA) is a novel subclass of noncoding-RNA which participate in progression of BCa. Here, we identified a novel circRNA-circ3323 and aimed to investigate the role of circ3323 in progression of BCa. Public data of RNA sequencing was used to identify significant circRNA related to BCa. The role of circRNAs in progression of BCa was assessed in cytotoxicity assay, transwell assay and flow cytometry. Biotin-coupled RNA pull-down and fluorescence in situ hybridization were performed to evaluate the interaction between circRNAs and miRNAs. The expression of circ3323 was higher in BCa tissues and cells than in normal samples. Experiments in vitro showed that the knockdown of circ3323 inhibited cell proliferation and impeded the metastasis of BCa cells. Mechanistically, we demonstrated that circ3323 acts as a sponge for miR-186-5p and promotes host gene APP's expression. Clinically, circ3323 predicts worse overall survival of BCa patients, indicating its prognostic value. Our study identified that circ3323 modulates metastasis of BCa through miR-186-5p/APP axis and may serve as a promising prognostic biomarker for BCa, which provides novel insights into treatment of BCa.
膀胱癌（BCa）是泌尿系统最常见的癌症，具有高复发率和预后不良的特点。环状 RNA（circRNA）是一种新型的非编码 RNA 分子，参与 BCa 的进展。在这里，我们鉴定了一种新型的 circRNA-circ3323，并旨在研究 circ3323 在 BCa 进展中的作用。我们使用公共 RNA 测序数据来鉴定与 BCa 相关的显著 circRNA。通过细胞毒性测定、transwell 测定和流式细胞术评估 circRNAs 在 BCa 进展中的作用。采用生物素偶联 RNA 下拉和荧光原位杂交来评估 circRNAs 和 miRNAs 之间的相互作用。circ3323 在 BCa 组织和细胞中的表达高于正常样本。体外实验表明，circ3323 的敲低抑制了 BCa 细胞的增殖和转移。机制上，我们证明 circ3323 作为 miR-186-5p 的海绵，并促进宿主基因 APP 的表达。临床上，circ3323 预测 BCa 患者的总生存期较差，表明其具有预后价值。我们的研究表明，circ3323 通过 miR-186-5p/APP 轴调节 BCa 的转移，可能作为 BCa 有前途的预后生物标志物，为 BCa 的治疗提供了新的见解。
