背景：以顺铂（DDP）为基础的联合化疗是治疗膀胱癌（BLca）的重要方法。顺铂化疗过程中容易出现化疗耐药，是BLca患者预后不良的重要原因之一。环状 RNA (circRNA) 因其在 BLca 的发展和进步中的作用而得到广泛认可。然而，circRNA 在 BLca 的 DDP 抗性中的确切作用仍不清楚。方法：为了研究 circATIC 的特性，采用了桑格测序、琼脂糖凝胶电泳和 RNase R/Actinomycin D 处理。 RT-qPCR 检测用于评估 BLca 组织和细胞中 circRNA、miRNA 和 mRNA 的表达水平。进行功能实验以评估 circATIC 在 BLca 进展和体外化疗敏感性中的功能。采用FISH、双荧光素酶报告基因测定、TRAP、RNA消化测定、RIP和ChIRP测定等多种技术来研究PTBP1、circATIC、miR-1247-5p和RCC2之间的关系。通过原位膀胱癌模型、异种皮下肿瘤模型和异种肺转移肿瘤模型来阐明circATIC在体内BLca进展和化疗敏感性中的功能和机制。结果：在我们的研究中，我们观察到 BLca 组织和细胞以及 DDP 耐药细胞中 circATIC 表达显着增强。 circATIC表达较高的患者肿瘤直径较大，术后转移发生率较高，总生存率较低。进一步的实验表明，circATIC 可加速 BLca 细胞的生长和转移，并诱导 DDP 耐药。从机制上讲，选择性剪接酶 PTBP1 介导 circATIC 的合成。 circATIC 可以通过海绵 miR-1247-5p 或构建 circATIC/LIN28A/RCC2 RNA-蛋白三元复合物来增强 RCC2 mRNA 稳定性。最后，circATIC 促进 RCC2 表达，增强上皮间质转化 (EMT) 进程并激活 JNK 信号通路，从而增强 BLca 细胞的 DDP 耐受性。结论：我们的研究表明，circATIC 促进 BLca 进展和 DDP 耐药，并且可以作为 BLca 治疗的潜在靶标。© 作者。

Background: Cisplatin (DDP) based combination chemotherapy is a vital method for the treatment of bladder cancer (BLca). Chemoresistance easily occurs in the course of cisplatin chemotherapy, which is one of the important reasons for the unfavorable prognosis of BLca patients. Circular RNAs (circRNAs) are widely recognized for their role in the development and advancement of BLca. Nevertheless, the precise role of circRNAs in DDP resistance for BLca remains unclear. Methods: To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. RT-qPCR assay was utilized to assess the expression levels of circRNA, miRNA and mRNA in BLca tissues and cells. Functional experiments were conducted to assess the function of circATIC in BLca progression and chemosensitivity in vitro. Various techniques such as FISH, Dual-luciferase reporter assay, TRAP, RNA digestion assay, RIP and ChIRP assay were used to investigate the relationships between PTBP1, circATIC, miR-1247-5p and RCC2. Orthotopic bladder cancer model, xenograft subcutaneous tumor model and xenograft lung metastasis tumor model were performed to indicate the function and mechanism of circATIC in BLca progression and chemosensitivity in vivo. Results: In our study, we observed that circATIC expression was significantly enhanced in BLca tissues and cells and DDP resistant cells. Patients with higher circATIC expression have larger tumor diameter, higher incidence of postoperative metastasis and lower overall survival rate. Further experiments showed that circATIC accelerated BLca cell growth and metastasis and induced DDP resistance. Mechanistically, alternative splicing enzyme PTBP1 mediated the synthesis of circATIC. circATIC could enhance RCC2 mRNA stability via sponging miR-1247-5p or constructing a circATIC/LIN28A/RCC2 RNA-protein ternary complex. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Conclusion: Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.© The author(s).