Hsa_circ_0008035 通过 miR-1184/RAP2B 轴抑制膀胱癌进展。
Hsa_circ_0008035 Knockdown Inhibits Bladder Cancer Progression through miR-1184/RAP2B Axis.
机构信息
Department of Urology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
出版信息
Urol Int. 2023;107(6):632-645. doi: 10.1159/000527873. Epub 2023 Mar 23.
INTRODUCTION
Circular RNAs (circRNAs) are related to the pathogenesis and progression of bladder cancer (BC). This research aimed to investigate the role and mechanism of hsa_circ_0008035 (circ_0008035) in BC progression.
METHODS
Circ_0008035, microRNA (miR)-1,184, and Ras-related protein 2B (RAP2B) levels were examined in BC via quantitative real-time polymerase chain reaction and Western blotting. Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, caspase-3 assay kit, transwell, and tube formation assays were conducted to estimate the effects of circ_0008035 on the malignant phenotypes of BC tumors. The interaction between RNAs and genes was evaluated via a dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model of BC in nude mice was established to estimate the effect of circ_0008035 in BC in vivo.
RESULTS
Circ_0008035 and RAP2B levels were upregulated, while miR-1184 abundance was downregulated in BC tissues and cells. Circ_0008035 knockdown constrained cell proliferation, migration, invasion and angiogenesis but promoted apoptosis in vitro. And circ_0008035 silencing curbed xenograft tumor growth in vivo. Circ_0008035 acted as a miRNA sponge for miR-1184. Circ_0008035 increased RAP2B expression by sponging miR-1184. MiR-1184 downregulation relieved the effects of circ_0008035 knockdown on BC progression. And RAP2B knockdown partly reversed the effects of miR-1184 overexpression on BC progression.
CONCLUSION
Circ_0008035-mediated BC progression via regulating the miR-1184/RAP2B axis, providing a potential target for BC treatment.
简介
环状 RNA（circRNAs）与膀胱癌（BC）的发病机制和进展有关。本研究旨在探讨 hsa_circ_0008035（circ_0008035）在 BC 进展中的作用和机制。
方法
通过定量实时聚合酶链反应和 Western blot 检测 BC 中 circ_0008035、microRNA（miR）-1、184 和 Ras 相关蛋白 2B（RAP2B）的水平。通过细胞计数试剂盒-8、集落形成、5-乙炔基-2'-脱氧尿苷染色、流式细胞术、半胱天冬酶-3 测定试剂盒、Transwell 和管形成测定评估 circ_0008035 对 BC 肿瘤恶性表型的影响。通过双荧光素酶报告和 RNA 免疫沉淀测定评估 RNA 与基因之间的相互作用。建立裸鼠 BC 异种移植模型，评估 circ_0008035 在体内对 BC 的影响。
结果
BC 组织和细胞中 circ_0008035 和 RAP2B 水平上调，而 miR-1184 丰度下调。circ_0008035 敲低抑制体外细胞增殖、迁移、侵袭和血管生成，但促进细胞凋亡。circ_0008035 沉默抑制体内异种移植肿瘤生长。circ_0008035 作为 miR-1184 的 miRNA 海绵。circ_0008035 通过海绵 miR-1184 增加 RAP2B 表达。miR-1184 下调缓解了 circ_0008035 敲低对 BC 进展的影响。RAP2B 敲低部分逆转了 miR-1184 过表达对 BC 进展的影响。
结论
circ_0008035 通过调节 miR-1184/RAP2B 轴介导 BC 进展，为 BC 治疗提供了一个潜在靶点。
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