尽管三阴性乳腺癌（TNBC）是一种常见的恶性肿瘤，但其发生和进展的分子机制仍不清楚。肿瘤相关巨噬细胞 (TAM) 通常会极化为促肿瘤表型，并与 TNBC 的不良预后相关。外泌体是细胞间通讯的重要介质，可以由供体细胞主动分泌以重新编程受体细胞。肿瘤细胞源性外泌体在 TNBC 进展和 TAM 重编程中的功能和分子机制亟待进一步探讨。我们证明，富含 miR-184-3p 的肿瘤细胞源性外泌体被巨噬细胞摄取，通过抑制 JNK 信号通路靶向EGR1，从而诱导巨噬细胞M2极化并协同促进肿瘤进展。载有癌基因 c-Myc 抑制剂 JQ1 的纳米颗粒可以通过减少巨噬细胞对 Rac1 相关外泌体的摄取来抑制极化过程。更重要的是，首次发现肿瘤抑制性miR-184-3p通过与RNA结合蛋白异源核糖核蛋白A2B1（hnRNPA2B1）结合主动分选到外泌体中，从而解除抑制，促进肿瘤细胞增殖和转移。 miR-184-3p 对 Mastermind-like 1 (MAML1) 的影响。在肿瘤细胞中过表达miR-184-3p，同时敲低hnRNPA2B1以阻止其通过外泌体分泌，可以有效抑制肿瘤生长和转移。我们的研究表明，hnRNPA2B1介导乳腺癌细胞中肿瘤抑制性miR-184-3p的外泌体转移巨噬细胞的作用是 TNBC 进展的重要介质，为 TNBC 的发病机制和治疗策略提供了新的见解。© 2023。作者。

Despite being a common malignant tumor, the molecular mechanism underlying the initiation and progression of triple-negative breast cancers (TNBCs) remain unclear. Tumor-associated macrophages (TAMs) are often polarized into a pro-tumor phenotype and are associated with a poor prognosis of TNBCs. Exosomes, important mediators of cell-cell communication, can be actively secreted by donor cells to reprogram recipient cells. The functions and molecular mechanisms of tumor cell-derived exosomes in TNBCs progression and TAMs reprogramming urgently need to be further explored.We demonstrated that tumor cell-derived exosomes enriched with miR-184-3p were taken up by macrophages to inhibit JNK signaling pathway by targeting EGR1, thereby inducing M2 polarization of macrophages and synergistically promoting tumor progression. Nanoparticles loaded with oncogene c-Myc inhibitor JQ1 could suppress the polarization process by reducing Rac1-related exosome uptake by macrophage. More importantly, it was found for the first time that tumor-suppressive miR-184-3p was actively sorted into exosomes by binding to RNA-binding protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), thus facilitating tumor cell proliferation and metastasis by relieving the inhibitory effect of miR-184-3p on Mastermind-like 1 (MAML1). Overexpressing miR-184-3p in tumor cells and simultaneously knocking down hnRNPA2B1 to block its secretion through exosomes could effectively inhibit tumor growth and metastasis.Our study revealed that hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p from breast cancer cells to macrophages was an important mediator of TNBCs progression, providing new insights into TNBCs pathogenesis and therapeutic strategies.© 2023. The Author(s).