CircCSNK1G1 Contributes to the Tumorigenesis of Gastric Cancer by Sponging miR-758 and Regulating ZNF217 Expression
Qiang Feng, Jinɡjinɡ Li
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.