Glioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real-time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan-Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit-8 (CCK-8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK-8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR-1304 and circ_0074026 or ERBB4 3'-untranslated region (3'-UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual-luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients' tumor size, WHO grade, disease-free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual-luciferase reporter assay demonstrated that miR-1304 interacted with circ_0074026 and ERBB4 3'-UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR-1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.
Keywords: ERBB4; circ_0074026; circular RNA; glioma; miR-1304.
© 2019 Wiley Periodicals, Inc.