p53野生型肺癌细胞能够发展出对辐射的耐药性。环状RNA （circRNA）由一系列具有独特结构的转录本组成。circRNA在肿瘤发生过程中起着关键作用，是潜在的生物标志物或治疗靶点。目前尚不清楚在p53野生型癌细胞中radiation之后circRNA的表达和功能是如何调控的。 使用CRISPR/Cas9将A549或H1299细胞分为p53-wt组和p53-KO组；这两组细胞都接受了4Gy的电离辐射（IR：p53-wt-IR和p53-KO-IR）。我们在体内进行了RNA-seq、CCK8、细胞周期和其他功能和机制实验。另外，我们还建立了p53基因敲除小鼠模型，以在体外测试细胞实验结果。 我们在不同组中发现了circRNA。circRNA_0006420（IRSense）在p53野生型细胞中上调，在辐射后与p53-KO细胞具有相同的表达水平，表明p53沉默可阻止其在辐射后的上调。在p53的存在下，辐射后上调的IRSense通过调节与DNA损伤修复（DDR）途径相关的蛋白质来诱导G2/M停滞。同时，辐射后上调的IRSense加重了辐射诱导的上皮间质转化（EMT）。有趣的是，在p53的存在下，它促进了IRSense/HUR/PTBP1复合物的形成，从而促进了辐射诱导的EMT。此外，c-Jun调控了辐照治疗后p53转录的上调。对于这些携带p53的肺癌细胞来说，上调的IRSense通过与核内的HUR（ElAV-like protein 1）和PTBP1（polypyrimidine tract-binding protein 1）相互作用，加重了肺癌细胞的增殖并增加了辐射耐药性。 保留p53的肺癌细胞可能会在辐射后上调circRNA_0006420（IRSense）的表达，形成IRSense/HUR/PTBP1复合物，导致放疗耐药性的发生。这项研究深化了我们对circRNA在调控放疗效应中作用的理解，并为有效的临床肺癌治疗提供了新的治疗途径。 版权所有 © 2023 Elsevier B.V. 由Elsevier B.V.制作和托管。

p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells.A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro.circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus.Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.Copyright © 2023. Production and hosting by Elsevier B.V.