WITHDRAWN: P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex

• DOI: 10.1016/j.jare.2023.07.011
• Publication Date: 2023-08-03T01:30:49Z
• Authors: Zhao Ju; Mingjun Lei; Lihui Xuan; Jinhua Luo; Meiling Zhou; Yin Wang; Liangfang Shen; Magdalena Skonieczna; Dmitry S. Ivanov; Hesham M.H. Zakaly; Vladimir Markovic; Pingkun Zhou; Ruixue Huang

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