肺癌是最常见的恶性肿瘤之一，在全球范围内的发病率和死亡率令人震惊。非小细胞肺癌（NSCLC）约占所有肺癌病例的80%-90%，是该疾病的主要病理表现，其5年生存率仅达到10%，令人不安。先前的大量研究表明，X 射线修复交叉互补基因 2 (XRCC2) 是一种关键的减数分裂基因，复杂地参与 DNA 损伤修复过程，其异常表达与肿瘤发生密切相关。然而，XRCC2 在 NSCLC 中的确切作用和潜在机制途径在很大程度上仍不清楚。在本研究中，我们发现 NSCLC 患者组织中 XRCC2 过度表达，特别是在与正常组织并置的高级别样本中。 XRCC2 的靶向敲低显着阻碍了 NSCLC 的体外和体内增殖。全面的 RNA 测序和流式救援测定表明，XRCC2 通过下调 FOS 表达来增强 NSCLC 细胞的增殖。此外，通过染色质免疫沉淀 (ChIP) 和荧光素酶报告基因检测，c-Myc 基因被明确鉴定为 XRCC2 转录因子，其中 c-Myc 表达的药理学减弱与多柔比星结合，在体外协同抑制 NSCLC 细胞生长和体内。总的来说，我们的研究结果为新型 c-Myc-XRCC2-FOS 轴促进 NSCLC 细胞增殖和多柔比星耐药性提供了重要见解，从而为 NSCLC 潜在的新诊断策略和治疗干预措施开辟了一条有希望的途径。版权所有 © 2024作者。由 Elsevier Masson SAS 出版。保留所有权利。

Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.