Liu Bingtao, Li Hongbin, Liu Xiongxiong, Li Feifei, Chen Weiqiang, Kuang Yanbei, Zhao Xueshan, Li Linying, Yu Boyi, Jin Xiaodong, Li Qiang
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China.
School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China.
Cell Signal. 2021 Aug;84:110012. doi: 10.1016/j.cellsig.2021.110012. Epub 2021 Apr 21.
Mounting evidence suggests that circular RNAs (circRNAs) are closely related to the regulation of gene expression during tumour development. However, the role of circRNAs in modulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells has not been explored.
Transcriptome sequencing was used to explore the expression profiles of circRNAs in NSCLC. The expression level of circRNAs was changed by inducing instantaneous knockdown or overexpression. Changes in proliferation and radiosensitivity of NSCLC cells were investigated using CCK-8, EDU, and clonal survivals.
By analysing the circRNA expression profile of NSCLC cells, we found that circRNA ZNF208 (circZNF208) was significantly upregulated in a radioresistant NSCLC cell line (A549-R11), which was acquired from the parental NSCLC cell line A549. Knockout experiments indicated that circZNF208 enhanced the radiosensitivity of A549 and A549-R11 cells to X-rays. Mechanistically, circZNF208 upregulated SNCA expression by acting as a sponge of miR-7-5p and subsequently promoted the resistance of NSCLC cells to low linear energy transfer (LET) X-rays. However, this effect was not observed in NSCLC cells exposed to high-LET carbon ions.
Knockdown of circZNF208 altered the radiosensitivity of patients with NSCLC to X-rays but did not significantly change the sensitivity to carbon ions. Therefore, circZNF208 might serve as a potential biomarker and therapeutic target for NSCLC treatment with radiotherapy of different modalities.
越来越多的证据表明，环状RNA（circRNA）与肿瘤发生过程中的基因表达调控密切相关。然而，circRNA在调节非小细胞肺癌（NSCLC）细胞放射敏感性中的作用尚未得到探索。
采用转录组测序技术探索NSCLC中circRNA的表达谱。通过瞬时敲低或过表达来改变circRNA的表达水平。使用CCK-8、EDU和克隆存活实验研究NSCLC细胞增殖和放射敏感性的变化。
通过分析NSCLC细胞的circRNA表达谱，我们发现circRNA ZNF208（circZNF208）在从亲本NSCLC细胞系A549获得的放射抗性NSCLC细胞系（A549-R11）中显著上调。敲除实验表明，circZNF208增强了A549和A549-R11细胞对X射线的放射敏感性。机制上，circZNF208通过作为miR-7-5p的海绵上调α-突触核蛋白（SNCA）的表达，随后促进NSCLC细胞对低线性能量传递（LET）X射线的抗性。然而，在暴露于高LET碳离子的NSCLC细胞中未观察到这种效应。
敲低circZNF208改变了NSCLC患者对X射线的放射敏感性，但对碳离子的敏感性没有显著改变。因此，circZNF208可能作为不同模式放射治疗NSCLC的潜在生物标志物和治疗靶点。
