摘要
背景:新兴研究表明,环状RNAs (circRNAs)在许多肿瘤的发生发展中发挥着重要作用。据报道,CircRNA-清道夫受体B类成员1 (Circ-SCARB1)是肾细胞癌(RCC)组织中升高的circRNA。本研究重点探讨了circSCARB1在肾细胞癌进展中的生物学功能和分子机制。 方法:采用实时定量聚合酶链反应(RT-PCR)和/或western blot检测Circ-SCARB1、microRNA (miR)-510-5p和syndecan 3 (SDC3)的表达。分别用3-(4,5)-二甲基噻唑(-z-y1)-3,5-二苯四氮唑和流式细胞术检测细胞增殖和凋亡。用Transwell法测定细胞迁移和侵袭性。miR-510-5p与Circ-SCARB1或SDC3之间的相互作用通过双荧光素酶报告基因检测得到验证。 结果:Circ-SCARB1在30对RCC组织和多个RCC细胞系中均有升高。Circ-SCARB1的下调抑制了细胞的增殖、迁移和侵袭,同时诱导细胞凋亡。MiR-510-5p被证实为Circ-SCARB1的靶点;通过沉默Circ-SCARB1抑制细胞进展是通过Circ-SCARB1和miR-510-5p之间的直接相互作用介导的。SDC3被证实是miR-510-5p的基因靶点;转染miR-510-5p mimic不仅抑制了SDC3的表达,也抑制了细胞的增殖,同时转染SDC3部分恢复了细胞的增殖。此外,Circ-SCARB1基因敲低降低了SDC3的表达,而anti-miR-510-5p的加入可以部分重新提高SDC3的表达。 结论:Circ-SCARB1通过抑制miR-510-5p和间接上调SDC3表达,促进RCC进展。这为研究肾细胞癌的发病机制和潜在的治疗靶点提供了一个新的视角。
关键词: CircRNA-清道夫受体B类成员1 (Circ-SCARB1),miR-510-5p,SDC3,肾细胞癌,进展,RCC细胞系。
Current Cancer Drug Targets
Title:CircRNA SCARB1 Promotes Renal Cell Carcinoma Progression Via Mir- 510-5p/SDC3 Axis
Volume: 20 Issue: 6
关键词: CircRNA-清道夫受体B类成员1 (Circ-SCARB1),miR-510-5p,SDC3,肾细胞癌,进展,RCC细胞系。
摘要:
Background: Emerging studies have indicated that circular RNAs (circRNAs) play important roles in the development of many tumors. CircRNA-scavenger receptor class B member 1 (Circ-SCARB1) was consistently reported as an elevated circRNA in RCC tissues. This study focused on examining the biological function and molecular mechanism of circSCARB1 in RCC progression.
Methods: Expressions of Circ-SCARB1, microRNA (miR)-510-5p, and syndecan 3 (SDC3) were detected using a quantitative real-time polymerase chain reaction (RT-PCR) and/or western blot. Cell proliferation and apoptosis were measured by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-diphenytetrazoliumromide and flow cytometry, respectively. Cell migration and invasion were measured using Transwell assays. The interaction between miR-510-5p and Circ-SCARB1 or SDC3 was verified using dual-luciferase reporter assays.
Results: Circ-SCARB1 was elevated in 30 pairs of RCC tissues and multiple RCC cell lines. Knockdown of Circ-SCARB1 inhibited cell proliferation, migration, and invasion while inducing cell apoptosis. MiR-510-5p was confirmed to be a target of Circ-SCARB1; inhibition of cell progression by silencing Circ-SCARB1 was mediated by a direct interaction between Circ-SCARB1 and miR-510-5p. SDC3 was verified to be a gene target of miR-510-5p; transfection of miR-510-5p mimic not only suppressed the expression of SDC3 but also the cell proliferation and an SDC3 cotransfection partially restored cell proliferation. Additionally, the genetic knockdown of Circ- SCARB1 reduced the expression SDC3, and the addition of anti-miR-510-5p could partially reelevate SDC3 expression.
Conclusion: Circ-SCARB1 promotes RCC progression via sequestering miR-510-5p and indirectly up-regulating SDC3 expression. This provides a novel perspective for the pathogenesis of RCC and potential therapeutic targets for the treatment of RCC.
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Cite this article as:
CircRNA SCARB1 Promotes Renal Cell Carcinoma Progression Via Mir- 510-5p/SDC3 Axis, Current Cancer Drug Targets 2020; 20 (6) . https://dx.doi.org/10.2174/1568009620666200409130032
DOI https://dx.doi.org/10.2174/1568009620666200409130032 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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