PDF(Pubmed)
Abstract：
Non-small cell lung cancer (NSCLC) is among the most prevalent cancers and a leading cause of cancer-related mortality globally. Extracellular vesicles (EVs) derived from NSCLC play a pivotal role in lung cancer progression. Our findings reveal a direct correlation between the abundance of EVs and the transfection efficiencies. Co-culturing two different lung cancer cell lines could enhance EVs formation, cell proliferation, migration and tumorigenicity. mRNA chip and metabolic analyses revealed significant alterations in the FOXO signaling pathway and unsaturated fatty acid metabolism within tumor tissues derived from co-cultured cells. Shotgun lipidomics studies and bioinformatics analyses guided our attention towards 4-Hydroxynonenal (4-HNE) and FOXO4. Elevating 4-HNE or FOXO4 levels could reduce the formation of EVs and impede cell growth and migration. While silencing FOXO4 expression lead to an increase in cell cloning rate and enhanced migration. These findings suggest that regulating the production of 4-HNE and FOXO4 might provide an effective therapeutic approach for the treatment of NSCLC.
摘要：
非小细胞肺癌（NSCLC）是全球最常见的癌症之一，也是导致癌症相关死亡的主要原因。源自NSCLC的细胞外囊泡(EV)在肺癌进展中起关键作用。我们的发现揭示了EV的丰度与转染效率之间的直接相关性。共培养两种不同的肺癌细胞系可以增强EV的形成，细胞增殖，迁移和致瘤性。mRNA芯片和代谢分析显示，来自共培养细胞的肿瘤组织中FOXO信号通路和不饱和脂肪酸代谢发生了显着变化。猎枪脂质组学研究和生物信息学分析引导我们关注4-羟基壬烯醛（4-HNE）和FOXO4。提高4-HNE或FOXO4水平可以减少EV的形成并阻碍细胞生长和迁移。而沉默FOXO4表达导致细胞克隆率增加和迁移增强。这些发现表明，调节4-HNE和FOXO4的产生可能为NSCLC的治疗提供有效的治疗方法。
