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环状 RNA_0058063 通过靶向 miR-486-3p/FOXP4 轴在膀胱癌进展中发挥 ceRNA 作用。

CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis.

机构信息

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.

出版信息

Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20193484.

Abstract

Emerging evidence has uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared with adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could act as a new biomarker and further developed to be a therapeutic target in BC.

摘要

新出现的证据揭示了环状 RNA(circRNAs)作为肿瘤发生和进展中的动态支架分子的关键调节作用。然而,hsa_circ_0058063(circRNA_0058063)在膀胱癌(BC)中的异常表达和临床意义仍知之甚少。通过微阵列分析在癌组织和非癌组织中分析 circRNA 的表达。通过荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验来揭示 circRNA_0058063 在 BC 中的功能。与相邻正常组织相比,BC 组织中 circRNA_0058063 表达上调。在 5637 和 BIU-87 细胞系中,circRNA_0058063 的敲低显著降低了细胞增殖和侵袭,并促进了细胞凋亡。此外,机制研究表明 circRNA_0058063 和 FOXP4 可以直接与 miR-486-3p 结合,表明 circRNA_0058063 通过与 miR-486-3p 竞争结合来调节 FOXP4 的表达。总之,circRNA_0058063 通过在 BC 进展中海绵吸附 miR-486-3p 发挥作用,可作为新的生物标志物,并进一步开发为 BC 的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8188/7103589/ef347cc09211/bsr-40-bsr20193484-g1.jpg

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