CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression

Abstract

Background An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma. Methods RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression. Results The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis. Conclusions CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.