Yang Lei, Zhou Yong-Ning, Zeng Miao-Miao, Zhou Nan, Wang Bin-Sheng, Li Bo, Zhu Xiao-Liang, Guan Quan-Lin, Chai Chen
Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
Department of Gastroenterology, The First hospital of Lanzhou University, Lanzhou, China.
Front Oncol. 2021 Oct 6;11:733745. doi: 10.3389/fonc.2021.733745. eCollection 2021.
Circular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.
CircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored and . Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.
Circ-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth . Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.
The circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.
环状RNA(circRNAs)与胃癌(GC)的发生和进展密切相关。我们旨在深入研究环状RNA-0002570(circ-0002570)在GC进展中的功能和病理机制。
利用生物信息学技术筛选出在GC中差异表达的circRNAs。采用qRT-PCR检测GC标本和细胞中circ-0002570的表达,并确定circ-0002570的预后价值。通过实验探究circ-0002570对GC细胞增殖、迁移和侵袭的功能作用。通过双荧光素酶报告基因检测、蛋白质印迹法和挽救实验证实circ-0002570、miR-587和VCAN之间的相互作用。
与相邻正常标本相比,circ-0002570在GC组织中的表达明显增加,circ-0002570表达较高的GC患者生存期较短。在功能上,敲低circ-0002570可抑制细胞增殖、迁移和侵袭,并抑制肿瘤生长。机制上,circ-0002570可吸附miR-587。miR-587可直接抑制NSCLC中VCAN的表达。circ-0002570的过表达可防止VCAN被miR-587介导的降解,从而促进GC进展。
circ-0002570-miR-587-VCAN调控通路促进了GC的进展。我们的研究结果为GC的诊断和治疗提供了潜在的新靶点。