Liu Chao, Yang Jing, Zhu Fengchi, Zhao Zhiying, Gao Lixue
Department of Gastroenterology, the No 2 Hospital of Baoding, Baoding City, 071051, Hebei, China.
Department of Anorectal Surgery, the No 2 Hospital of Baoding, Baoding City, 071051, Hebei, China.
Biochem Genet. 2022 Dec;60(6):1895-1913. doi: 10.1007/s10528-021-10180-6. Epub 2022 Feb 9.
Gastric cancer (GC) is the fifth most common cancer, which has a significant impact on human health. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of GC, but the mechanism still indistinct. In this work, we explored the roles of circ_0001190 in GC. The levels of circ_0001190, microRNA-586 (miR-586) and sclerostin domain containing 1 (SOSTDC1) were detected by quantitative RT-PCR and western blot in GC. The cell functions were scrutinized by cell counting kit-8 assay, 5-Ethynyl-29-deoxyuridine assay, flow cytometry assay, tube formation assay, transwell assay, and western blot. Furthermore, the relationship between miR-586 and circ_0001190 or SOSTDC1 was identified by dual-luciferase reporter assay. Finally, the xenograft model test was implemented to demonstrate the effect of exosomal circ_0001190 in vivo. The levels of circ_0001190 and SOSTDC1 were downregulated, and the miR-586 level was increased in GC. For functional assay, circ _0001190 overexpression inhibited cell vitality, cell proliferation, angiogenesis, cell migration and invasion, whereas stimulated cell apoptosis in GC cells. Circ _0001190 served as a miR-586 sponge to adjust the expression of SOSTDC1. Additionally, miR-586 could promote the advancement of GC by interfering SOSTDC1. Exosomal circ_0001190 overexpression inhibited the development of GC by miR-586/SOSTDC1 axis, which proposed a potential targeted therapy for GC cure.
胃癌（GC）是第五大常见癌症，对人类健康有重大影响。最近的研究表明，环状RNA（circRNAs）可能影响胃癌的进展，但其机制仍不清楚。在这项工作中，我们探讨了circ_0001190在胃癌中的作用。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测了胃癌组织中circ_0001190、微小RNA-586（miR-586）和含硬化蛋白结构域1（SOSTDC1）的水平。通过细胞计数试剂盒-8检测、5-乙炔基-2'-脱氧尿苷检测、流式细胞术检测、管腔形成检测、Transwell检测和蛋白质免疫印迹法对细胞功能进行了研究。此外，通过双荧光素酶报告基因检测确定了miR-586与circ_0001190或SOSTDC1之间的关系。最后，进行了异种移植模型试验，以证明外泌体circ_0001190在体内的作用。在胃癌中，circ_0001190和SOSTDC1的水平下调，而miR-586水平升高。在功能试验中，circ_0001190过表达抑制了胃癌细胞的活力、细胞增殖、血管生成、细胞迁移和侵袭，同时促进了细胞凋亡。Circ_0001190作为miR-586的海绵来调节SOSTDC1的表达。此外，miR-586可通过干扰SOSTDC1促进胃癌进展。外泌体circ_0001190过表达通过miR-586/SOSTDC1轴抑制了胃癌的发展，为胃癌治疗提出了一种潜在的靶向治疗方法。
