J Cancer 2021; 12(11):3354-3366. doi:10.7150/jca.54934 This issue
Department of Rehabilitation, Children's Hospital of Nanjing Medical University, Jiangsu, China.
Objective: Previous studies have demonstrated that circular RNAs (circRNAs) play vital roles in pathological process of various diseases, including tumors. This study aimed at exploring the role and mechanism of circRNA RNA ZNF609 (circ-ZNF609) in the occurrence and development of glioma.
Materials and methods: Real-time quantitative PCR (qRT-PCR) was applied to measure the expression of circ-ZNF609, miRNA-1224-3p (miR-1224-3p) and Polo-like kinase 1 (PLK1) in glioma tissues and cell lines. Furthermore, the association between circ-ZNF609 and clinical features of glioma was analyzed. CCK8 assay, EdU assay and Transwell assay were conducted to detect the effect of circ-ZNF609, miR-1224-3p and PLK1 on proliferation, migration and invasion in glioma cells. Then, we investigated the underlying mechanism of circ-ZNF609 by bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP), qRT-PCR and western blotting assay.
Results: Circ-ZNF609 was confirmed prominently upregulated in glioma. Inhibition of circ-ZNF609 could obviously suppress glioma cell proliferation, migration and invasion, while overexpression of circ-ZNF609 promoted glioma growth and metastasis. In vivo, xenotransplanted tumor model also showed that overexpression of circ-ZNF609 could promote in vivo glioma growth. Mechanistically, circ-ZNF609 could promote PLK1 expression via binding to miR-1224-3p, circ-ZNF609/miR-1224-3p/PLK1 was shown responsible for circ-ZNF609 promoting glioma growth and metastasis.
Conclusion: Together, our results revealed that circ-ZNF609 elevates glioma growth and metastasis via enforcing PLK1 expression by competitively binding miR-1224-3p, suggesting that circ-ZNF609 might be an underlying therapeutic target for glioma.
Keywords: circular RNA ZNF609, glioma, miRNA sponge, malignant progression