Qiang Feng, Li Jingjing
Department of Gastroenterology, the First People's Hospital of Huzhou, Huzhou, 313000, People's Republic of China.
Cancer Manag Res. 2021 Jun 28;13:5027-5038. doi: 10.2147/CMAR.S305767. eCollection 2021.
Increasing evidence indicates that circular RNAs (circRNAs) act as vital regulators in various cancers. Nevertheless, the effect of circCSNK1G1 on gastric cancer (GC) is still unknown.
The mRNA levels of circCSNK1G1, miR-758, and ZNF217 were measured by RT-qPCR. The protein levels of ZNF217 were evaluated by Western blotting. Cell migration, invasion, proliferation, and apoptosis were detected by Transwell, CCK-8, and flow cytometry assays. The association between miR-758 and circCSNK1G1/ZNF217 was confirmed by RIP and luciferase reporter assays. Xenograft assay was employed for in vivo experiment.
In the current study, it was demonstrated that the expression levels of circCSNK1G1 and ZNF217 were upregulated in GC tissues and cells, while the level of miR-758 was declined. Furthermore, functional assays indicated that circCSNK1G1 depletion suppressed GC progression in vitro and in vivo. In addition, circCSNK1G1 directly interacted with miR-758, and the supplementation of miR-758 suppressed the development of GC, which was abolished following pcDNA3.1-circCSNK1G1 transfection. Then, we explored the downstream mechanism of miR-758 and found that miR-758 could target the 3'UTR of ZNF217 mRNA. The overexpression of miR-758 neutralized the ZNF217-mediated effects on facilitating the progression of GC. Finally, we revealed that circCSNK1G1 could upregulate ZNF217 expression by sponging miR-758 in GC cells.
Our study revealed that circCSNK1G1 accelerated GC progression via the miR-758/ZNF217 axis, suggesting that circCSNK1G1 might be a potential biomarker for GC diagnosis and treatment.
越来越多的证据表明，环状RNA（circRNAs）在多种癌症中发挥着重要的调节作用。然而，circCSNK1G1对胃癌（GC）的影响仍不清楚。
采用RT-qPCR检测circCSNK1G1、miR-758和ZNF217的mRNA水平。通过蛋白质印迹法评估ZNF217的蛋白质水平。采用Transwell、CCK-8和流式细胞术检测细胞迁移、侵袭、增殖和凋亡。通过RIP和荧光素酶报告基因检测证实miR-758与circCSNK1G1/ZNF217之间的关联。采用异种移植试验进行体内实验。
在本研究中，结果表明circCSNK1G1和ZNF217的表达水平在GC组织和细胞中上调，而miR-758的水平下降。此外，功能试验表明，circCSNK1G1的缺失在体外和体内均抑制了GC的进展。此外，circCSNK1G1直接与miR-758相互作用，miR-758的补充抑制了GC的发展，而在转染pcDNA3.1-circCSNK1G1后这种抑制作用被消除。然后，我们探索了miR-758的下游机制，发现miR-758可以靶向ZNF217 mRNA的3'UTR。miR-758的过表达抵消了ZNF217介导促进GC进展作用。最后，我们发现circCSNK1G1可以通过在GC细胞中海绵化miR-758来上调ZNF217的表达。
我们的研究表明，circCSNK1G1通过miR-758/ZNF217轴加速GC进展，提示circCSNK1G1可能是GC诊断和治疗的潜在生物标志物。
