NCOA4 mediated ferritinophagy induced ferroptosis regulates radiosensitivity and prognosis of glioma

Abstract Aims Gliomas are generally resistant to ionizing radiation. Ferroptosis is an important cause of cancer cell death caused by ionizing radiation. However, it is not clear how ferroptosis regulates the radiosensitivity of glioma. Methods In vitro, we verified the effect of ferroptosis on radiosensitivity of glioma cells, and tested the effect of NCOA4-mediated ferritinophagy on ferroptosis. The effect of NCOA4 on the prognosis of glioma patients treated with radiotherapy was analyzed using public databases, and the possible action pathways of NCOA4 were analyzed by bioinformatics. In vivo experiments, we again verified the effect of ferroptosis on radiosensitivity of glioma and the radiosensitivity change of glioma after knocking down NCOA4. Results We have demonstrated through experiments that both ferroptosis and autophagy promote the radiosensitivity of glioma cells. Bioinformatics analysis shows that ferritinophagy selective cargo receptor NCOA4 is highly expressed in gliomas with good prognosis, while patients with low expression of NCOA4 have poor prognosis after radiotherapy. Meanwhile, through experimental verification, low expression of NCOA4 is associated with poor prognosis in gliomas, while high expression is associated with good prognosis. Through analysis of the NCOA4 related pathways, we demonstrate that NCOA4 regulates the radiosensitivity and prognosis of gliomas by regulating the key gene ACSL4 for ferroptosis sensitivity. Ferroptosis promotes radiosensitivity in gliomas and is dependent on NCOA4 mediated ferritinophagy.