The biological functions of circular RNAs (circRNAs) in gastric cancer (GC) remain largely unexplored. Here, we identified that circ-RanGAP1 was significantly upregulated in both GC tissues and exosomes from the plasma of GC patients. High circ-RanGAP1 expression was closely associated with an advanced TNM stage, lymph node metastases, and worse survival. Inhibition of circ-RanGAP1 decreased GC cell invasion and migration in vitro. Overexpression of circ-RanGAP1 had the opposite effect. Additionally, circ-RanGAP1 silencing remarkably suppressed tumor growth and metastasis of GC in vivo. Mechanistically, circ-RanGAP1 sponged miR-877-3p to upregulate VEGFA expression. Overexpression of miR-877-3p reversed the biological functions mediated by circ-RanGAP1 in GC cells. Interestingly, we demonstrated that circ-RanGAP1 was upregulated in plasma exosomes from preoperative GC patients. More importantly, the plasma exosomes derived from these patients enhanced the migration and invasion potential of GC cells. Overall, the circ-RanGAP1-mediated miR-877-3p/VEGFA axis promotes GC progression. Our findings suggest that circ-RanGAP1 might act as a potential prognostic biomarker and therapeutic target for GC treatment.

中文翻译：

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环状 RNA circ-RanGAP1 通过靶向 miR-877-3p 调节 VEGFA 表达促进胃癌侵袭和转移。

环状RNA（circRNA）在胃癌（GC）中的生物学功能在很大程度上仍未被探索。在这里，我们发现 circ-RanGAP1 在 GC 组织和来自 GC 患者血浆的外泌体中均显着上调。高 circ-RanGAP1 表达与晚期 TNM 分期、淋巴结转移和较差的生存率密切相关。circ-RanGAP1 的抑制降低了体外 GC 细胞的侵袭和迁移。circ-RanGAP1 的过表达具有相反的效果。此外，circ-RanGAP1的沉默显着抑制了体内GC的肿瘤生长和转移。从机制上讲，circ-RanGAP1 吸附 miR-877-3p 以上调 VEGFA 表达。miR-877-3p的过表达逆转了GC细胞中circ-RanGAP1介导的生物学功能。有趣的是，我们证明了 circ-RanGAP1 在术前 GC 患者的血浆外泌体中上调。更重要的是，来自这些患者的血浆外泌体增强了 GC 细胞的迁移和侵袭潜力。总体而言，circ-RanGAP1 介导的 miR-877-3p/VEGFA 轴促进 GC 进展。我们的研究结果表明，circ-RanGAP1 可能作为 GC 治疗的潜在预后生物标志物和治疗靶点。