环状 RNA 0000419 通过调控 miR-300/RGMB 轴在胃癌发展中发挥肿瘤抑制作用。
Circ_0000419 acts as a tumor suppressor in gastric cancer development via regulating miR-300/RGMB axis.
机构信息
Department of Gastrointestinal Surgery, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, No. 1882 Zhonghuan South Road, Jiaxing, Zhejiang, China.
出版信息
Int J Clin Oncol. 2023 Nov;28(11):1475-1485. doi: 10.1007/s10147-023-02379-x. Epub 2023 Jul 20.
OBJECTIVE
Dysregulated circular RNAs (circRNAs) have been verified to function in the development of gastric cancer (GC). The current study was designed to investigate the role of circ_0000419 in GC progression, and the potential mechanistic pathway.
METHODS
Relative expression of circ_0000419, microRNA-300 (miR-300) and Repulsive Guidance Molecule B (RGMB) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Cell metastasis, including migration and invasion, was assessed by wound healing and Transwell assays. Glucose consumption and lactate production were examined using kits. The association between miR-300 and circ_0000419 or RGMB was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Role of circ_0000419 in vivo was determined by xenograft experiment.
RESULTS
Circ_0000419 and RGMB were downregulated, while miR-300 was upregulated in GC tissues and cells. Gain of circ_0000419 inhibited migration, invasion and glycolysis in GC cells, which was attenuated by introduction of miR-300 or silencing of RGMB. Circ_0000419 sponged miR-300, and RGMB was direct target of miR-300. Circ_0000419 overexpression could block GC tumor growth in vivo.
CONCLUSION
Circ_0000419 inhibited GC cell migration, invasion and glycolysis through regulation of miR-300/RGMB axis, at least in part, affording a molecular target for GC treatment.
目的
失调的环状 RNA（circRNAs）已被证实参与胃癌（GC）的发展。本研究旨在探讨 circ_0000419 在 GC 进展中的作用及其潜在的机制途径。
方法
通过定量逆转录聚合酶链反应（qRT-PCR）分析 circ_0000419、microRNA-300（miR-300）和排斥性导向分子 B（RGMB）的相对表达。通过划痕愈合和 Transwell 测定评估细胞迁移和侵袭。使用试剂盒检测葡萄糖消耗和乳酸生成。通过双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）实验验证 miR-300 与 circ_0000419 或 RGMB 的关联。通过异种移植实验确定 circ_0000419 在体内的作用。
结果
circ_0000419 和 RGMB 在 GC 组织和细胞中下调，而 miR-300 上调。circ_0000419 的获得抑制了 GC 细胞的迁移、侵袭和糖酵解，而引入 miR-300 或沉默 RGMB 则减弱了这种抑制作用。circ_0000419 吸附 miR-300，而 RGMB 是 miR-300 的直接靶标。circ_0000419 的过表达可以在体内抑制 GC 肿瘤的生长。
结论
circ_0000419 通过调节 miR-300/RGMB 轴抑制 GC 细胞的迁移、侵袭和糖酵解，至少部分地为 GC 治疗提供了一个分子靶点。
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