非小细胞肺癌（NSCLC）是一种普遍存在的侵袭性恶性肿瘤，治疗选择有限。尽管治疗取得了进步，非小细胞肺癌仍然是全世界癌症相关死亡的主要原因。肿瘤异质性和治疗耐药性给实现缓解带来了挑战。需要进行研究来提供分子见解、确定新靶点并开发个性化疗法以改善结果。在公共数据库和 NSCLC 组织微阵列中探讨了 DHX38 在 NSCLC 中的蛋白表达水平和预后价值。建立 DHX38 敲低和过表达细胞系以评估 DHX38 在 NSCLC 中的作用。进行体外和体内功能实验以评估增殖和转移。为了确定 DHX38 在人类 NSCLC 中的潜在分子机制，通过 IP 分离了与 DHX38 相互作用的蛋白质，并通过 LC-MS 进行了鉴定。 DHX38 相互作用蛋白的 KEGG 分析揭示了 DHX38 在人类 NSCLC 中的分子通路。通过蛋白质印迹分析和免疫组织化学 (IHC) 染色验证异常通路激活。分子特异性抑制剂进一步用于探索非小细胞肺癌的潜在治疗靶点。通过免疫共沉淀（co-IP）实验验证了与DHX38相互作用的通路相关靶点。在DHX38稳定过表达的细胞系中，敲低目标蛋白，探讨其对DHX38过表达诱导的肿瘤促进的补充作用。NSCLC中DHX38蛋白表达增加，DHX38高表达水平的患者预后不良。体外和体内实验表明DHX38促进人NSCLC细胞的增殖、迁移和侵袭。 DHX38过表达导致MAPK通路异常激活并促进肿瘤中上皮间质转化（EMT）。 SCH772984 是一种新型特异性 ERK1/2 抑制剂，可显着减少 DHX38 过表达引起的细胞增殖、迁移和侵袭的增加。 co-IP 实验证实 DHX38 与 Ras GTPase 激活蛋白结合蛋白 G3BP1 相互作用。 DHX38 调节 G3BP1 的表达。在 DHX38 稳定过表达的细胞中敲低 G3BP1 可阻止 DHX38 诱导的肿瘤细胞增殖、迁移和侵袭。沉默G3BP1可逆转DHX38过表达诱导的MAPK通路激活和EMT。在NSCLC中，DHX38充当肿瘤启动子。 DHX38 调节 G3BP1 表达，导致 MAPK 信号通路激活，从而促进肿瘤细胞增殖、转移和非小细胞肺癌上皮间质转化 (EMT) 的进展。版权所有 © 2023。由 Elsevier Inc 出版。

Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy with limited therapeutic options. Despite advances in treatment, NSCLC remains a major cause of cancer-related death worldwide. Tumor heterogeneity and therapy resistance present challenges in achieving remission. Research is needed to provide molecular insights, identify new targets, and develop personalized therapies to improve outcomes.The protein expression level and prognostic value of DHX38 in NSCLC were explored in public databases and NSCLC tissue microarrays. DHX38 knockdown and overexpression cell lines were established to evaluate the role of DHX38 in NSCLC. In vitro and in vivo functional experiments were conducted to assess proliferation and metastasis. To determine the underlying molecular mechanism of DHX38 in human NSCLC, proteins that interact with DHX38 were isolated by IP and identified by LC-MS. KEGG analysis of DHX38-interacting proteins revealed the molecular pathway of DHX38 in human NSCLC. Abnormal pathway activation was verified by Western blot analysis and immunohistochemical (IHC) staining. A molecule-specific inhibitor was further used to explore potential therapeutic targets for NSCLC. The pathway-related target that interacted with DHX38 was verified by co-immunoprecipitation(co-IP) experiments. In cell lines with stable DHX38 overexpression, the target protein was knocked down to explore its complementary effect on DHX38 overexpression-induced tumor promotion.The protein expression of DHX38 was increased in NSCLC, and patients with high DHX38 expression levels had a poor prognosis. In vitro and in vivo experiments showed that DHX38 promoted the proliferation, migration and invasion of human NSCLC cells. DHX38 overexpression caused abnormal activation of the MAPK pathway and promoted epithelial-mesenchymal transition (EMT) in tumours. SCH772984, a novel specific ERK1/2 inhibitor, significantly reduced the increases in cell proliferation, migration and invasion caused by DHX38 overexpression. The co-IP experiments confirmed that DHX38 interacted with the Ras GTPase-activating protein-binding protein G3BP1. DHX38 regulated the expression of G3BP1. Knocking down G3BP1 in cells with stable DHX38 overexpression prevented DHX38-induced tumor cell proliferation, migration and invasion. Silencing G3BP1 reversed the MAPK pathway activation and EMT induced by DHX38 overexpression.In NSCLC, DHX38 functions as a tumor promoter. DHX38 modulates G3BP1 expression, leading to the activation of the MAPK signaling pathway, thus promoting tumor cell proliferation, metastasis, and the progression of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer.Copyright © 2023. Published by Elsevier Inc.