The Novel circRNA_0022587/miR-216a-5p/PRKCE Axis Restricts Glioblastoma (GBM) Progression

GBM is the most common primary neuroepithelial tumor in adults, characterized by an extremely poor clinical prognosis. The roles and mechanisms by which circRNAs regulate biological behaviors associated with GBM remain poorly understood. In this study, quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were employed to determine the cellular localization as well as the expression regulatory relationships within the circRNA-0022587/miR-216a-5p/PRKCE axis. Dual-luciferase reporter assays along with RNA pulldown experiments confirmed direct binding interactions among these molecules. Additionally, CCK-8 assays, wound-healing assays, Transwell invasion assays, Western blotting analyses, and immunohistochemistry (IHC) were conducted to investigate how this axis affects GBM biological behaviors both in vitro and in vivo. circRNA_0022587 is significantly downregulated GBM cell lines and predominantly localized in the cytoplasm. By acting as a competing endogenous RNA (ceRNA), circRNA_0022587 sequesters miR-216a-5p, thereby relieving its inhibitory effect on PRKCE and leading to increased PRKCE expression at both mRNA and protein levels. Activation of the circRNA_0022587/miR-216a-5p/PRKCE axis suppresses GBM cell proliferation and migration in vitro and in vivo. Mechanistic analyses further demonstrate that this functional inhibition is mediated through the modulation of key proliferation markers (PCNA and Ki-67) and epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin and E-cadherin). Our findings indicate that this axis inhibits GBM progression by precisely regulating proteins associated with proliferation and migration, representing a potential novel therapeutic direction for treating GBM.