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

CircFOXO3 functions as a molecular sponge for miR-143-3p to promote the progression of gastric carcinoma via upregulating USP44.

机构信息

Department of Clinical Laboratory Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.

Department of Gastrointestinal Surgery, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.

出版信息

Gene. 2020 Aug 30;753:144798. doi: 10.1016/j.gene.2020.144798. Epub 2020 May 20.

DOI:10.1016/j.gene.2020.144798
PMID:32445925
Abstract

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.

摘要

胃癌(GC)在癌症发病率中排名第五,在癌症相关死亡中排名第三,在全球范围内造成了巨大的健康和经济负担。GC 形成和发展的分子机制仍不清楚。我们的目的是确定环状 RNA circFOXO3 在 GC 中的作用,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促进作用。circFOXO3 增强了 GC 细胞的体外增殖和迁移能力,并促进了 GC 细胞在体内的肿瘤生长。生物信息学分析表明,circFOXO3 可能通过特异性结合 microRNA(miR)-143-3p 来调节 USP44 的表达。环状 RNA circFOXO3-miR-143-3p-USP44 轴在 GC 细胞中的存在通过 RNA 结合蛋白免疫沉淀、荧光素酶报告基因检测和 RNA 下拉实验得到了证实。所有数据表明,circFOXO3 通过靶向 miR-143-3p 上调 USP44 的表达促进 GC 细胞的增殖和迁移。

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