AEG-1 Knockdown Sensitizes Glioma Cells to Radiation Through Impairing Homologous Recombination Via Targeting RFC5.

Abstract

Radiotherapy is the most important adjuvant treatment for glioma; however, radioresistance is the major cause for inevitable recurrence and poor survival of glioma patients. Thus, this study aims to investigate the effect of astrocyte elevated gene-1 (AEG-1) on the radiosensitivity of glioma cells. Immunohistochemistry assay found that AEG-1 was generally overexpressed in glioma tissues and was correlated with poor clinicopathological features of glioma patients. AEG-1 knockdown inhibited proliferation of glioma cells. And γ-H2AX foci assay, colony formation assay, and flow cytometry analysis demonstrated that AEG-1 depletion enhanced radiosensitivity and promoted apoptosis as well as cell cycle arrest in G2 phase of glioma cells treated by ionizing radiation. Moreover, replication factor C5 (RFC5) was screened as the target of AEG-1 by using Affymetrix human gene expression array, and RFC5 expression was downregulated in AEG-1 knockdown glioma cells. Mechanistically, AEG-1 knockdown impaired homologous recombination repair activity induced by radiation through inhibiting RFC5 expression. Furthermore, the Kaplan-Meier analysis and multivariate Cox regression analysis indicated that high levels of AEG-1 and RFC5 were related to poor prognosis of glioma patients treated with radiotherapy. Taken together, our findings indicate that AEG-1 may serve as a reliable radiosensitizing target for glioma radiotherapy.