Papillary thyroid carcinoma (PTC), comprising 85% of all thyroid cancers, is an epithelial malignancy. The potential for malignant transformation in normal cells by thyroid cancer cells via exosomal Annexin A1 (ANXA1) delivery is investigated in this study. Our aim is to determine the impact of PTC cells on macrophage polarization through exosomal ANXA1 secretion and its implications for tumor progression. Exosomes in PTC cells were examined using transmission electron microscopy, exosome labeling, and nanoparticle tracking analysis. Real-time quantitative polymerase chain reaction was employed to quantify gene expression levels. Protein levels were determined through Western blot analysis. The interplay between genes was assessed using luciferase reporter and RNA pull-down assays. Functional experiments were conducted to investigate PTC cell proliferation and apoptosis. Our findings reveal that ANXA1 promotes PTC cell proliferation and inhibits apoptosis. Exosomes derived from PTC cells were found to promote macrophage M2 polarization. ANXA1 stimulates M2 polarization through the activation of the PI3K/AKT pathway. MicroRNA-374a-5p (miR-374a-5p) and microRNA-374b-5p (miR-374b-5p) were identified as inhibitors of ANXA1 expression and PI3K/AKT pathway activity, thereby inhibiting macrophage M2 polarization. Furthermore, miR-374a-5p and miR-374b-5p were observed to suppress PTC cell proliferation through their regulatory action on ANXA1. Our study suggests that miR-374a/b-5p inhibits PTC cell growth by blocking the macrophage M2 polarization induced by exosomal ANXA1.

甲状腺乳头状癌 (PTC) 占所有甲状腺癌的 85%，是一种上皮恶性肿瘤。本研究调查了甲状腺癌细胞通过外泌体膜联蛋白 A1 (ANXA1) 递送对正常细胞进行恶性转化的可能性。我们的目的是确定 PTC 细胞通过外泌体 ANXA1 分泌对巨噬细胞极化的影响及其对肿瘤进展的影响。使用透射电子显微镜、外泌体标记和纳米颗粒跟踪分析检查 PTC 细胞中的外泌体。采用实时定量聚合酶链反应来量化基因表达水平。通过蛋白质印迹分析确定蛋白质水平。使用荧光素酶报告基因和 RNA Pull-down 测定来评估基因之间的相互作用。进行功能实验来研究 PTC 细胞增殖和凋亡。我们的研究结果表明，ANXA1 促进 PTC 细胞增殖并抑制细胞凋亡。研究发现源自 PTC 细胞的外泌体可促进巨噬细胞 M2 极化。 ANXA1 通过激活 PI3K/AKT 通路刺激 M2 极化。 MicroRNA-374a-5p (miR-374a-5p) 和 microRNA-374b-5p (miR-374b-5p) 被确定为 ANXA1 表达和 PI3K/AKT 通路活性的抑制剂，从而抑制巨噬细胞 M2 极化。此外，观察到 miR-374a-5p 和 miR-374b-5p 通过对 ANXA1 的调节作用抑制 PTC 细胞增殖。我们的研究表明，miR-374a/b-5p 通过阻断外泌体 ANXA1 诱导的巨噬细胞 M2 极化来抑制 PTC 细胞生长。