Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Cell Biol Toxicol. 2023 Oct;39(5):1-18. doi: 10.1007/s10565-022-09715-3. Epub 2022 May 14.
Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 (hsa_circ_0000615) has been shown to serve as an oncogene in all kinds of solid tumors and may act as the novel biomarker in tumor diagnosis and therapy in tumor early diagnosis and therapy. However, the underlying character and mechanism of circZNF609 in cisplatin chemosensitivity and bladder cancer (BCa) development were unknown. The expression level of cell division cycle 25B (CDC25B), microRNA 1200 (miR-1200), and circZNF609 in BCa cells and tissues depended on quantitative real-time PCR (qRT-PCR). CDC25B protein level was assayed with Western blot. Functional assays in vitro and in vivo had been conducted to inspect the important role of circZNF609 on BCa progression and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200, and CDC25B. Mechanistic exploration was confirmed by RNA pull-down assay, RNA fluorescence in situ hybridization (FISH) and Dual luciferase reporter assay. CircZNF609 expression was increased significantly in BCa cell lines and tissues. For BCa patients, increased expression of circZNF609 was correlated with a worse survival. In vitro and in vivo, enforced expression of circZNF609 enhanced BCa cells proliferation, migration, and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to act as a new diagnostic biomarker and therapeutic target in BCa. Enhancing cisplatin sensitivity is an important direction for bladder cancer management. 1. This research reveals that circZNF609 improves bladder cancer progression and inhibits cisplatin sensitivity by inducing G1/S cell cycle arrest via a novel miR-1200/CDC25B cascades. 2. CircZNF609 was confirmed associated with worse survival of bladder cancer patients. 3. CircZNF609 act as a prognostic biomarker for bladder cancer treatment.
环状 RNA（circRNAs）在肿瘤的发生和治疗中得到了广泛的研究。CircZNF609（hsa_circ_0000615）已被证明在各种实体瘤中作为癌基因发挥作用，并且可能作为肿瘤早期诊断和治疗中肿瘤诊断和治疗的新型生物标志物。然而，circZNF609 在顺铂化疗敏感性和膀胱癌（BCa）发展中的潜在特征和机制尚不清楚。通过定量实时 PCR（qRT-PCR）检测 BCa 细胞和组织中细胞分裂周期蛋白 25B（CDC25B）、微小 RNA 1200（miR-1200）和 circZNF609 的表达水平。使用 Western blot 测定 CDC25B 蛋白水平。体外和体内功能测定用于检测 circZNF609 对 BCa 进展和 BCa 顺铂化疗敏感性的重要作用。使用 RNA 测序和在线数据库预测 circZNF609、miR-1200 和 CDC25B 之间的相互作用。通过 RNA 下拉测定、RNA 荧光原位杂交（FISH）和双荧光素酶报告基因测定证实了机制探索。CircZNF609 的表达在 BCa 细胞系和组织中显著增加。对于 BCa 患者，circZNF609 的高表达与生存不良相关。在体外和体内，circZNF609 的强制表达增强了 BCa 细胞的增殖、迁移和顺铂化疗耐药性。机制上，circZNF609 通过海绵吸附 miR-1200 减轻了对靶 CDC25B 表达的抑制作用。CircZNF609 通过新型 circZNF609/miR-1200/CDC25B 轴促进肿瘤生长，表明 circZNF609 具有作为 BCa 新的诊断生物标志物和治疗靶点的显著潜力。提高顺铂敏感性是膀胱癌管理的一个重要方向。1. 这项研究揭示了 circZNF609 通过诱导新型 miR-1200/CDC25B 级联反应引起 G1/S 细胞周期停滞，从而提高膀胱癌的进展并抑制顺铂敏感性。2. 已证实 circZNF609 与膀胱癌患者的生存不良相关。3. circZNF609 可作为膀胱癌治疗的预后生物标志物。
