Expression profiles and potential functions of circular RNAs in extracellular vesicles isolated from radioresistant glioma cells

Abstract

The molecular mechanisms of circular RNAs (circRNAs) in extracellular vesicles (EVs) associated with glioma radioresistance remain unknown. The aim of the present study was to assess the differential circRNA expression profiles between EVs isolated from U251 cells and EVs isolated from radioresistant U251 (RR‑U251) cells. Identified circRNAs in EVs isolated from RR‑U251 cells (RR‑EVs) act as a U251 microRNA (miRNA) sponge. The circRNA expression was determined using RNA sequencing (RNA-seq) technique. A total of 1,235 circRNAs were detected. We identified 63 upregulated and 48 downregulated circRNAs in RR‑EVs compared with those from U251 cells (Nor‑EVs). The expression level of candidate circATP8B4 was confirmed using real‑time quantitative PCR. It was significantly higher in RR‑EVs than in Nor‑EVs. Expression profile of RR‑U251 and U251 miRNAs was conducted. miRanda and RNAhybrid softwares was used to predict the U251 downregulated miRNAs interacting with circATP8B4. CircATP8B4 from RR‑EVs may be transferred to normal glioma U251 cells and act as an miR‑766 sponge to promote cell radioresistance. In conclusion, using RNA‑seq and bioinformatics, it was found that circATP8B4 in RR‑EVs acts as a U251 miR‑766 sponge, which may be involved in glioma radioresistance.