特发性肺纤维化（IPF）是一种与增加肺癌风险相关的进展性老年肺部疾病。尽管先前的研究已经表明IPF会恶化肺癌患者的生存状况，但IPF是否独立影响癌症的恶性程度和预后仍然没有定论。近期，细胞外囊泡（EVs）已经成为分子生物标志物和肺部稳态和病理生理学间细胞间通讯的主要介质。EV运载的纤维母细胞 - 肿瘤细胞通讯可能通过调节多个信号通路参与肺癌的发展和进展。在本研究中，我们研究了来自IPF微环境中肺纤维母细胞（LF）分泌的EV对非小细胞肺癌（NSCLC）恶性程度的影响。我们发现，来自IPF患者的LF具有肌成纤维细胞分化和细胞衰老的表型。此外，我们发现IPF LF分泌的EV的微RNA（miRNA）组成明显改变，并对NSCLC细胞具有促进增殖的功能。机械上，该表型主要归因于IPF LF EV中miR-19a的富集。作为下游信号通路，IPF LF EV中的miR-19a通过调节ZMYND11介导的c-Myc激活在NSCLC中发挥作用，可能有助于IPF患者的NSCLC患者的不良预后。我们的发现为了解IPF微环境中肺癌进展提供了新的机制洞察。因此，阻止IPF LF EV miR-19a及其信号通路的分泌是管理IPF和肺癌进展的潜在治疗策略。

Idiopathic pulmonary fibrosis (IPF) is a progressive aging-related lung disease that is associated with increased lung cancer risk. Although previous studies have shown that IPF worsens the survival of lung cancer patients, whether IPF independently affects cancer malignancy and prognosis remains inconclusive. Extracellular vesicles (EVs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication in lung homeostasis and pathogenesis. EV cargo-mediated fibroblast-tumor cell communication might participate in the development and progression of lung cancer by modulating various signaling pathways. In this study, we examined the impact of lung fibroblast (LF)-derived EVs on non-small cell lung cancer (NSCLC) malignancy in the IPF microenvironment. Here, we showed that LFs derived from IPF patients have phenotypes of myofibroblast differentiation and cellular senescence. Furthermore, we found that IPF LF-derived EVs have markedly altered microRNA (miRNA) compositions and exert pro-proliferative functions on NSCLC cells. Mechanistically, the phenotype was attributed mainly to an enrichment of miR-19a in IPF LF-derived EVs. As a downstream signaling pathway, mir-19a in IPF LF-derived EVs regulates ZMYND11-mediated c-Myc activation in NSCLC, potentially contributing to the poor prognosis of NSCLC patients with IPF. Our discoveries provide novel mechanistic insights for understanding lung cancer progression in the IPF microenvironment. Accordingly, blocking the secretion of IPF LF-derived EV miR-19a and their signaling pathways is a potential therapeutic strategy for managing IPF and lung cancer progression.