Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR‐1304 to modulate ERBB4 expression

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. 1. circ_0074026 is elevated in glioma and correlates with an unfavorable prognosis. 2. circ_0074026 promotes glioma cell progression. 3. circ_0074026 level does not affect normal human astrocyte (NHA) cell growth and apoptosis. 4. circ_0074026 sponges miR‐1304 to upregulate ERBB4 expression in glioma. 5. circ_0074026 facilitates cell proliferation and invasion and inhibits cell apoptosis through upregulating ERBB4.