有越来越多的证据表明，外泌体介导的microRNA(miRNA)传递有助于连接与肿瘤相关的巨噬细胞和癌细胞，包括肺腺癌(LUAD)细胞。为了确定miR-3153在LUAD进展和M2巨噬细胞极化中的作用并探索其调节机制，进行了相关的分子机制分析和机械验证。随后进行了体外功能性测定和体内实验，以评估外泌体介导的M2巨噬细胞极化和LUAD进展的作用。LUAD细胞通过外泌体传递miR-3153。异质核糖核蛋白A2B1 (HNRNPA2B1) 促进miR-3153生物合成和外泌体分选。外泌体miR-3153靶向锌指蛋白91(ZFP91)，抑制畸形样激酶1(MINK1)的泛素化和降解，从而激活c-Jun N端激酶(JNK)信号通路并诱导M2巨噬细胞极化。由LUAD细胞分泌的外泌体诱导的M2巨噬细胞极化促进了LUAD细胞的恶性进程。LUAD细胞通过外泌体传递miR-3153激活JNK信号通路，诱导M2巨噬细胞极化，从而促进LUAD的进展。©作者(们) 2023。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至: journals.permissions@oup.com。

There is increasing evidence that exosome-mediated transmission of microRNA (miRNAs) helps to connect tumor-associated macrophages and cancer cells, including lung adenocarcinoma (LUAD) cells.To identify the role of miR-3153 in LUAD progression and M2 macrophage polarization and explore its regulatory mechanism.The relevant molecular mechanisms were analyzed and validated through mechanistic assays. In vitro functional assays followed by in vivo experiments were implemented to evaluate the role of exosomes in mediating M2 macrophage polarization and LUAD progression.LUAD cells transmitted miR-3153 through exosomes. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) promoted miR-3153 biosynthesis and exosomal sorting. Exosomal miR-3153 targeted zinc finger protein 91 (ZFP91) to suppress the ubiquitination and degradation of misshapen-like kinase 1 (MINK1), thereby activating the c-Jun N-terminal kinase (JNK) signaling pathway and inducing M2 macrophage polarization. M2 macrophage polarization induced by LUAD cell-derived exosomes promoted the malignant process of LUAD cells.Transmission of exosomal miR-3153 by LUAD cells activates the JNK signaling pathway and induces M2 macrophage polarization, thus promoting the progression of LUAD.© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.