Gastric carcinoma (GC) ranks fifth in terms of cancer morbidity and third in cancer-related death worldwide and imposes enormous health and economic burdens. The molecular mechanisms underlying GC formation and progression remain unclear. Our aim was to identify the involvement of circular RNA circFOXO3 in GC, and to determine the underlying mechanisms. In this study, we revealed a stimulatory role of circular RNA circFOXO3 in tumor growth in vivo. CircFOXO3 enhanced GC cell proliferation and migration in vitro and promoted tumor growth of GC cells in vivo. Bioinformatic analysis revealed that circFOXO3 might regulate USP44 expression by specifically binding to microRNA (miR)-143-3p. Existence of circFOXO3-miR-143-3p-USP44 axis in GC cells was confirmed by RNA-binding protein immunoprecipitation, luciferase reporter assay, and an RNA pull-down experiments. All the data indicate that circFOXO3 promotes GC cell proliferation and migration by upregulating USP44 expression via targeting of miR-143-3p.

中文翻译：

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CircFOXO3充当miR-143-3p的分子海绵，通过上调USP44促进胃癌的进展。

胃癌（GC）在全球癌症发病率方面排名第五，在与癌症相关的死亡方面排名第三，并给健康和经济负担带来了巨大负担。GC形成和发展的分子机制尚不清楚。我们的目的是鉴定环状RNA circFOXO3与GC的关系，并确定其潜在机制。在这项研究中，我们揭示了环状RNA circFOXO3在体内肿瘤生长中的刺激作用。CircFOXO3在体外增强了GC细胞的增殖和迁移，并在体内促进了GC细胞的肿瘤生长。生物信息学分析表明，circFOXO3可能通过与microRNA（miR）-143-3p特异性结合来调节USP44表达。通过RNA结合蛋白免疫沉淀，荧光素酶报告基因分析，RNA印迹法证实了GC细胞中circFOXO3-miR-143-3p-USP44轴的存在。以及RNA下拉实验。所有数据表明，circFOXO3通过靶向miR-143-3p上调USP44表达来促进GC细胞增殖和迁移。