环状 RNA 119872 通过调控 miR-622/G3BP1 轴及其下游信号通路促进葡萄膜黑色素瘤的发展。
Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways.
机构信息
Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, HB, China.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, HB, China.
出版信息
J Exp Clin Cancer Res. 2021 Feb 12;40(1):66. doi: 10.1186/s13046-021-01833-w.
BACKGROUND
The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored.
METHODS
The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting.
RESULTS
We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways.
CONCLUSIONS
Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM.
背景
环状 RNA（circRNAs）在葡萄膜黑色素瘤（UM）中的异常表达已经被揭示出来，但它们与 UM 发展相关的具体潜在分子机制尚未被充分探索。
方法
通过实时定量 PCR（qRT-PCR）和 Western blot 分析检测 UM 细胞系和组织中 circ_0119872、G3BP1 和 miR-622 的水平。进行体外和体内实验研究 circ_0119872 对 UM 细胞发生的作用。使用生物信息学工具预测 circ_0119872、miR-622 和 G3BP1 之间的关系，并通过 RNA-FISH、RNA 下拉和双荧光素酶报告基因实验进行验证。通过基因集富集分析（GSEA）和 Western blot 确定 circ_0119872 对 Wnt/β-catenin 和 mTOR 信号通路的影响。
结果
我们发现 circ_0119872 在 UM 细胞系和组织中上调。此外，circ_0119872 的过表达促进了 UM 细胞的恶性转化，而 circ_0119872 的沉默则抑制了它。此外，circ_0119872 可以直接与 miR-622 相互作用，作为 miRNA 海绵，调节 miR-622 靶基因 G3BP1 的表达以及下游 Wnt/β-catenin 和 mTOR 信号通路。
结论
circ_0119872 可能通过一种新型的 circ_0119872/miR-622/G3BP1 轴在 UM 中发挥癌基因作用，激活 Wnt/β-catenin 和 mTOR 信号通路，这可能为 UM 的管理提供潜在的生物标志物和治疗靶点。
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