The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation

• DOI: 10.3389/fcell.2021.650819
• Publication Date: 2021-05-14T09:19:14Z
• Authors: Qiong Wang; Yangyang Chen; Haiyan Chang; Ting Hu; Jue Wang; Yuxiu Xie; Jing Cheng
• Keywords: Radioresistance; Radiosensitivity; Mitotic catastrophe

Objective: This study aimed to investigate the effect of ataxia telangiectasia mutated (ATM)–mediated autophagy on radiosensitivity lung cancer cells under low-dose radiation and further role ATM its specific mechanism in transition from hyper-radiosensitivity (HRS) induced radioresistance (IRR). Methods: The changes HRS/IRR phenomenon A549 H460 were verified by colony formation assay. Changes phosphorylation cell different low doses examined western blot, polymerase chain reaction (PCR), electron microscopy. expression was knocked down short interfering RNA (siRNA) transfection, ATM-regulated molecules related pathways screened transcriptome sequencing analysis. detection results PCR blot. differential metabolites assay nude mouse xenograft model used verify experiments. Results: (1) with high showed positive HRS/IRR, whereas negative HRS/IRR. After decreased, HRS increased, also increased. associated increase autophagy-related phosphorylated c-Jun N-terminal kinase (p-JNK) autophagy/Beclin 1 regulator (AMBRA1). (2) DL -Norvaline, a product carbon metabolism cells, inhibited radiation. -Norvaline increased levels ATM, JNK, AMBRA1 cells. (3) Mouse experiments confirmed regulatory function Conclusion: may influence through p-JNK participate regulation phenomenon. Autophagy interacts cellular metabolite regulating