Lung cancer remains notorious for its poor prognosis. Despite the advent of tyrosine kinase inhibitors and immune checkpoint inhibitors, the probability of curing the disease in lung cancer patients remains low. Novel mechanisms and treatment strategies are needed to provide hope to patients. Advanced strategies of next generation sequencing (NGS) and bioinformatics were used to analyze normal and lung cancer tissues from lung cancer patients. Amine oxidases have been linked to leukocyte migration and tumorigenesis. However, the roles of amine oxidases in lung cancer are not well‑understood. Our results indicated that amine oxidase, copper containing 3 (AOC3) was significantly decreased in the tumor tissue compared with the normal tissue, at both the mRNA and protein level, in the included lung cancer patients and public databases. Lower expression of AOC3 conferred a poorer survival probability across the different cohorts. Epigenetic silencing of AOC3 via miR‑3691‑5p caused tumor promotion and progression by increasing migration and epithelial‑mesenchymal transition (EMT). Furthermore, knockdown of AOC3 caused less CD4⁺ T‑cell attachment onto lung cancer cells and reduced transendothelial migration in vitro, as well as reducing CD4⁺ T‑cell trafficking to the lung in vivo. In conclusion, the present study revealed that downregulation of AOC3 mediated lung cancer promotion and progression, as well as decrease of immune cell recruitment. This novel finding could expand our understanding of the dysregulation of the tumor immune microenvironment and could help to develop a novel strategy for the treatment of lung cancer.

中文翻译：

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胺氧化酶，含铜 3 发挥抗间充质转化并增强 CD4+ T 细胞募集以延长肺癌的生存期。

肺癌因其预后不良而臭名昭著。尽管出现了酪氨酸激酶抑制剂和免疫检查点抑制剂，但肺癌患者治愈这种疾病的可能性仍然很低。需要新的机制和治疗策略来为患者带来希望。使用新一代测序 (NGS) 和生物信息学的先进策略来分析肺癌患者的正常和肺癌组织。胺氧化酶与白细胞迁移和肿瘤发生有关。然而，胺氧化酶在肺癌中的作用尚不清楚。我们的结果表明，在肺癌患者和公共数据库中，与正常组织相比，在 mRNA 和蛋白质水平上，肿瘤组织中含铜 3 的胺氧化酶（AOC3）显着降低。AOC3 的较低表达在不同的队列中赋予较差的生存概率。通过 miR-3691-5p 的 AOC3 表观遗传沉默通过增加迁移和上皮间充质转化 (EMT) 导致肿瘤促进和进展。此外，AOC3 的敲低导致 CD4 减少⁺ T 细胞附着在肺癌细胞上并减少体外跨内皮迁移，以及减少体内CD4 ⁺ T 细胞向肺的转运。总之，本研究表明，AOC3 的下调介导了肺癌的促进和进展，以及免疫细胞募集的减少。这一新发现可以扩大我们对肿瘤免疫微环境失调的理解，并有助于制定治疗肺癌的新策略。