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

objectiveGlioma (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

methodsCircRNA 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 3'-UTR. Rescue assay was finally conducted to explore whether the oncogenic role of circ-ELF2 was partially attributed to miR-510-5p/MUC15 signaling.

resultsWe 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.

conclusionThis study indicates that circ-ELF2/miR-510-5p/MUC15 signaling plays a key role in promoting the occurrence and development of GM.