Knockdown of circ_0008344 contributes to radiosensitization in glioma via miR-433-3p/RNF2 axis

Abstract

Numerous studies have identified that circular RNAs (circRNAs) functioned as important regulators in tumor initiation, carcinogenesis, drug or radiation resistance. This study aims to reveal the function of circ_0008344 on radiosensitivity in glioma. The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for detecting the circ_0008344 and microRNA-433-3p (miR-433-3p) levels. Cell survival intensity and apoptosis were analyzed through colony formation assay and flow cytometry respectively. The protein levels were examined via Western blot. Dual-luciferase reporter assay was exploited for the analysis of target combination. Xenograft models were established in mice for circ_0008344 research in vivo. Our data showed that circ_0008344 level was signally increased in radioresistant glioma tissues and its down-regulation facilitated the susceptibility of glioma cells to radiation. Additionally, we found that circ_0008344 could interact with miR-433-3p and regulated radiosensitivity of glioma cells via sponging miR-433-3p. Ring finger protein 2 (RNF2) was proved to be a target of miR-433-3p and it was regulated by circ_0008344/miR-433-3p axis. The promotion of circ_0008344 knockdown on radiosensitivity was counteracted by RNF2 overexpression in glioma cells. Further experiment in vivo indicated that circ_0008344 down-regulation inhibited glioma growth and acted on miR-433-3p/RNF2 axis to enhance the radiosensitivity in glioma. These evidences manifested that knockdown of circ_0008344 exerted the radiosensitivity-promoting effect on glioma via the miR-433-3p-mediated RNF2 down-regulation, identifying circ_0008344 as a novel diagnostic biomarker of radioresistance and therapeutic target in glioma radiotherapy.