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.

背景：新兴研究表明，环状 RNA（circRNA）在许多肿瘤的发展中起着重要作用。CircRNA 清道夫受体 B 类成员 1（Circ-SCARB1）一直被报道为 RCC 组织中升高的 circRNA。本研究的重点是检查 circSCARB1 在 RCC 进展中的生物学功能和分子机制。

方法：使用定量实时聚合酶链反应 (RT-PCR) 和/或蛋白质印迹检测 Circ-SCARB1、microRNA (miR)-510-5p 和 Syndecan 3 (SDC3) 的表达。细胞增殖和凋亡分别通过 3-(4, 5)-二甲基噻唑 (-z-y1)-3, 5-diphenytetrazoliumromide 和流式细胞术测量。使用 Transwell 测定法测量细胞迁移和侵袭。miR-510-5p 和 Circ-SCARB1 或 SDC3 之间的相互作用使用双荧光素酶报告基因检测进行验证。

结果：Circ-SCARB1 在 30 对 RCC 组织和多个 RCC 细胞系中升高。敲除 Circ-SCARB1 可抑制细胞增殖、迁移和侵袭，同时诱导细胞凋亡。MiR-510-5p 被确认为 Circ-SCARB1 的目标；通过沉默 Circ-SCARB1 抑制细胞进展是由 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；miR-510-5p 模拟物的转染不仅抑制了 SDC3 的表达，而且还抑制了细胞增殖，SDC3 共转染部分恢复了细胞增殖。此外，Circ-SCARB1 的基因敲低降低了 SDC3 的表达，添加抗 miR-510-5p 可以部分重新提高 SDC3 的表达。

结论：Circ-SCARB1 通过隔离 miR-510-5p 和间接上调 SDC3 表达促进 RCC 进展。这为 RCC 的发病机制和 RCC 治疗的潜在治疗靶点提供了新的视角。