非小细胞肺癌（NSCLC）占肺癌病例的大部分，占80%以上。 EV 中的 RNA 在细胞外囊泡 (EV) 介导的各种生物学和病理过程中发挥着关键作用。长非编码RNA (lncRNA) 与癌症相关功能广泛相关，包括细胞增殖、迁移、侵袭和耐药性。肿瘤相关巨噬细胞被认为是肿瘤发生的关键贡献者。鉴于这些见解，本研究旨在揭示 lncRNA NORAD 对 NSCLC 细胞系和 NSCLC 异种移植小鼠模型中 M2 巨噬细胞衍生的 EV 的影响。根据其形态和特定生物标志物，对 EV 进行了精心分离和验证。使用免疫沉淀研究了 lncRNA NORAD 和 SMIM22 之间的相互作用。在 NSCLC 细胞系中评估了 EV 中 SMIM22/GALE 或 lncRNA NORAD 对糖酵解的影响。此外，我们通过集落形成和流式细胞术测定评估了 EV 中 M2 巨噬细胞衍生的 lncRNA NORAD 对细胞增殖和凋亡的影响。此外，使用异种移植肿瘤动物模型证实了 EV 中 M2 巨噬细胞衍生的 lncRNA NORAD 对肿瘤生长的影响。结果强调了 M2 巨噬细胞衍生的 lncRNA NORAD 在 NSCLC EV 中的潜在作用。 SMIM22/GALE 促进 NSCLC 细胞的糖酵解和增殖。此外，EV 中的 lncRNA NORAD 靶向 NSCLC 细胞中的 SMIM22 和 miR-520g-3p。值得注意的是，EV 中的 lncRNA NORAD 促进 NSCLC 细胞的增殖，并通过 miR-520g-3p 轴促进 NSCLC 肿瘤的生长。总之，EV 中 M2 巨噬细胞衍生的 lncRNA NORAD 通过 miR-520g-3p/SMIM22/GALE 轴促进 NSCLC 进展。© 2024。作者。

Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, accounting for over 80%. RNAs in EVs play a pivotal role in various biological and pathological processes mediated by extracellular vesicle (EV). Long non-coding RNAs (lncRNAs) are widely associated with cancer-related functions, including cell proliferation, migration, invasion, and drug resistance. Tumor-associated macrophages are recognized as pivotal contributors to tumorigenesis. Given these insights, this study aims to uncover the impact of lncRNA NORAD in EVs derived from M2 macrophages in NSCLC cell lines and xenograft mouse models of NSCLC. EVs were meticulously isolated and verified based on their morphology and specific biomarkers. The interaction between lncRNA NORAD and SMIM22 was investigated using immunoprecipitation. The influence of SMIM22/GALE or lncRNA NORAD in EVs on glycolysis was assessed in NSCLC cell lines. Additionally, we evaluated the effects of M2 macrophage-derived lncRNA NORAD in EVs on cell proliferation and apoptosis through colony formation and flow cytometry assays. Furthermore, the impact of M2 macrophage-derived lncRNA NORAD in EVs on tumor growth was confirmed using xenograft tumor animal models. The results underscored the potential role of M2 macrophage-derived lncRNA NORAD in EVs in NSCLC. SMIM22/GALE promoted glycolysis and the proliferation of NSCLC cells. Furthermore, lncRNA NORAD in EVs targeted SMIM22 and miR-520g-3p in NSCLC cells. Notably, lncRNA NORAD in EVs promoted the proliferation of NSCLC cells and facilitated NSCLC tumor growth through the miR-520g-3p axis. In conclusion, M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression through the miR-520g-3p/SMIM22/GALE axis.© 2024. The Author(s).