Zhao Wei, Wu Yudan, Wang Yixiao, Li Tongyi, Liu Qiuyan, Hou Zhiping
School of Basic Medical Sciences, Chengde Medical University, Chengde, China.
Affiliated Hospital of Chengde Medical University, Chengde, China.
Med Oncol. 2025 Mar 10;42(4):96. doi: 10.1007/s12032-025-02635-2.
Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms globally. Its development and metastasis are closely associated with the polarization of macrophages within the tumor microenvironment (TME). In particular, the polarization of M2-type macrophages has been demonstrated to be related to the promotion of tumor growth, migration, and angiogenesis. This study aims to investigate the role of miR-92a-3p in colon cancer-derived exosomes in regulating M2-type macrophage polarization by targeting EID2B and to elucidate the impact of this process on tumor migration and angiogenesis. MicroRNAs that were differentially expressed in plasma exosomes from CRC patients were initially identified through a search of the GEO database. The results were then verified by RT-qPCR using miR-92a-3p. The uptake of exosomes was observed via laser confocal microscopy, and the impact of miR-92a-3p on the polarization of exosomes and macrophages was examined through the use of RT-qPCR and WB. A bioinformatics analysis and a dual-luciferase reporter assay were employed to identify the downstream target of miR-92a-3p and to investigate its effect on the MAPK/ERK pathway. miR-92a-3p was upregulated in plasma exosomes of colon cancer patients and exhibited a positive correlation with lymph node metastasis. The results demonstrated that miR-92a-3p was capable of promoting M0 macrophage polarization toward the M2 phenotype, and of enhancing the migratory and invasive capacities of CRC cells, as well as their angiogenic potential in vitro. Bioinformatic analysis and experimental validation demonstrated that miR-92a-3p targeted EID2B and that this target gene was negatively correlated with M2-type macrophage polarization. The results demonstrated that miR-92a-3p promotes macrophage M2 polarization by activating the MAPK/ERK pathway. miR-92a-3p activates the MAPK/ERK pathway and induces macrophage M2 polarization by targeting EID2B, thereby promoting migration and angiogenesis in CRC. These findings offer new potential targets for the treatment of colon cancer.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。其发生发展和转移与肿瘤微环境（TME）中巨噬细胞的极化密切相关。特别是，已证明M2型巨噬细胞的极化与肿瘤生长、迁移和血管生成的促进有关。本研究旨在探讨结肠癌来源外泌体中的miR-92a-3p通过靶向EID2B在调节M2型巨噬细胞极化中的作用，并阐明这一过程对肿瘤迁移和血管生成的影响。通过搜索GEO数据库初步鉴定了CRC患者血浆外泌体中差异表达的微小RNA。然后使用miR-92a-3p通过RT-qPCR验证结果。通过激光共聚焦显微镜观察外泌体的摄取，并通过RT-qPCR和WB检测miR-92a-3p对外泌体和巨噬细胞极化的影响。采用生物信息学分析和双荧光素酶报告基因检测来鉴定miR-92a-3p的下游靶点，并研究其对MAPK/ERK信号通路的影响。miR-92a-3p在结肠癌患者血浆外泌体中上调，且与淋巴结转移呈正相关。结果表明，miR-92a-3p能够促进M0巨噬细胞向M2表型极化，并增强CRC细胞的迁移和侵袭能力以及其体外血管生成潜力。生物信息学分析和实验验证表明，miR-92a-3p靶向EID2B，且该靶基因与M2型巨噬细胞极化呈负相关。结果表明，miR-92a-3p通过激活MAPK/ERK信号通路促进巨噬细胞M2极化。miR-92a-3p通过靶向EID2B激活MAPK/ERK信号通路并诱导巨噬细胞M2极化，从而促进CRC的迁移和血管生成。这些发现为结肠癌的治疗提供了新的潜在靶点。
