DEAD-box螺旋酶1（DDX1）在数种人类癌症中具有致癌特性。然而，DDX1在非小细胞肺癌（NSCLC）中的临床意义和生物学角色仍不清楚。在这里，我们检查了DDX1在NSCLC中的化疗相关性。我们使用UALCAN数据库，Western blot分析，免疫组化和RT-qPCR检测方法，评估DDX1在NSCLC细胞系（H1650和A549）和患者组织中的表达。利用克隆形成，CCK-8，流式细胞术，划痕愈合，Transwell，肿瘤球形成和免疫染色检测方法以及裸鼠移植瘤模型确定DDX1在NSCLC细胞化疗敏感性和潜在机制中的作用。我们的研究表明DDX1在NSCLC细胞系和组织中过表达。我们进一步发现，去除DDX1增加了NSCLC细胞对化疗药物顺铂的敏感性，增加了细胞凋亡，并抑制了细胞迁移和侵袭。共免疫沉淀实验表明，DDX1结合到ADAR1，并增加了ADAR1蛋白表达。此外，我们发现ADAR1通过结合到RAC3mRNA而介导了促癌作用，与去氨基酶活性无关。我们的研究结果不仅表明DDX1通过ADAR1/RAC3轴介导顺铂的化疗敏感性，而且强调ADARs作为细胞稳态和癌症进展中的必需RNA结合蛋白的重要性。我们的结果提示DDX1在人类NSCLC的发展和进展中发挥重要作用，并且DDX1可能作为NSCLC患者的治疗靶点。版权所有©2023。由Elsevier Inc.发表。

DEAD-box helicase 1 (DDX1) has oncogenic properties in several human cancers. However, the clinical significance and biological role of DDX1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we examined the chemotherapeutic relevance of DDX1 in NSCLC.We used the UALCAN database, Western blot analysis, and immunohistochemical and RT-qPCR assays to assess DDX1 expression in NSCLC cell lines (H1650 and A549) and patient tissues. The role of DDX1 in the chemosensitivity of NSCLC cells and the underlying mechanisms were determined using colony formation, CCK-8, flow cytometry, wound healing, Transwell, tumor sphere formation, and immunostaining assays, together with a xenograft tumor model in nude mice.Our study revealed that DDX1 was overexpressed in NSCLC cell lines and tissues. We further found that depleting DDX1 increased the sensitivity of NSCLC cells to the chemotherapy drug cisplatin, increased cell apoptosis, and inhibited cell migration and invasion. Co-immunoprecipitation assays revealed that DDX1 bound to ADAR1, and increased ADAR1 protein expression. Furthermore, we found that ADAR1 mediated cancer-promoting effects, independent of deaminase activity, by binding to RAC3 mRNA. Our findings not only show that DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis but also highlight the importance of ADARs as essential RNA-binding proteins for cell homeostasis, as well as cancer progression.Our results suggest that DDX1 plays an important role in the development and progression of human NSCLC and that DDX1 may serve as a therapeutic target in NSCLC patients.Copyright © 2023. Published by Elsevier Inc.