Circ-ELF2 Acts as a Competing Endogenous RNA to Facilitate Glioma Cell Proliferation and Aggressiveness by Targeting MiR-510-5p/MUC15 Signaling

OBJECTIVE: Glioma (GM) is a common type of malignant and aggressive tumor in brain with poor prognosis. Circular RNAs (circRNAs) are well-known regulators in cancer progression. However, its molecular basis in GM remains to be investigated. MATERIALS AND METHODS: CircRNA microarray was used to detect differentially expressed circRNAs in GM and matched noncancerous tissues. qRT-PCR was applied to detect the expression profile of circ-ELF2 in GM tissue specimens and cell lines. CCK-8, clone formation, AO/EB staining, flow cytometry, wound healing, and transwell assays were performed to identify the functions of circ-ELF2 in GM cells. The distribution of circ-ELF2 was analyzed by RNA-FISH and subcellular fractionation assay. Dual-luciferase reporter assay was applied to verify the predicted binding sites between miR-510-5p and circ-ELF2/MUC15 3ʹ-UTR. Rescue assay was finally conducted to explore whether the oncogenic role of circ-ELF2 was partially attributed to miR-510-5p/MUC15 signaling. RESULTS: We observed that circ-ELF2 was significantly upregulated in GM tissues, which was analyzed by circRNA microarray and qRT-PCR. Upregulation of circ-ELF2 was associated with poor prognosis and high recurrence rate for GM patients after surgery. The collapse of circ-ELF2 caused growth arrest and downregulation of cell migratory and invasive potential of GM cells and promoted cell apoptosis. In contrast, elevated expression of circ-ELF2 led to the opposite effect. Mechanistically, circ-ELF2 acted as a competing endogenous RNA (ceRNA) for miR-510-5p to positive modulate MUC15 expression at posttranscriptional level. Circ-ELF2 upregulated MUC15 by sponging miR-510-5p, thus promoting GM growth and aggressiveness. CONCLUSION: This study indicates that circ-ELF2/miR-510-5p/MUC15 signaling plays a key role in promoting the occurrence and development of GM.