Department of Respiratory Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Hum Mol Genet. 2023 Jun 19;32(13):2162-2176. doi: 10.1093/hmg/ddad052.
There is increasing evidence that exosome-mediated transmission of microRNAs helps to connect tumor-associated macrophages and cancer cells, including lung adenocarcinoma (LUAD) cells. The objective of this study is 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 promoted miR-3153 biosynthesis and exosomal sorting. Exosomal miR-3153 targeted zinc finger protein 91 to suppress the ubiquitination and degradation of misshapen-like kinase 1, 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.
越来越多的证据表明，外泌体介导的 microRNAs 传递有助于连接肿瘤相关巨噬细胞和癌细胞，包括肺腺癌 (LUAD) 细胞。本研究旨在确定 miR-3153 在 LUAD 进展和 M2 巨噬细胞极化中的作用，并探讨其调节机制。通过机制研究对相关分子机制进行了分析和验证。通过体外功能测定和体内实验评估了外泌体在介导 M2 巨噬细胞极化和 LUAD 进展中的作用。LUAD 细胞通过外泌体传递 miR-3153。异质核核糖核蛋白 A2B1 促进 miR-3153 的生物合成和外泌体分选。外泌体 miR-3153 靶向锌指蛋白 91，抑制畸形样激酶 1 的泛素化和降解，从而激活 c-Jun N 端激酶 (JNK) 信号通路，诱导 M2 巨噬细胞极化。由 LUAD 细胞衍生的外泌体诱导的 M2 巨噬细胞极化促进了 LUAD 细胞的恶性进程。LUAD 细胞传递的外泌体 miR-3153 激活 JNK 信号通路并诱导 M2 巨噬细胞极化，从而促进 LUAD 的进展。
