Exosome-derived miR-372-5p promotes stemness and metastatic ability of CRC cells by inducing macrophage polarization

• Published in: Cellular signalling 2023-11, Vol.111, p.110884-110884, Article 110884
• Main Authors: Shi, Xiuru, Wei, Ke, Wu, Yulun, Mao, Lingyu, Pei, Wenhao, Zhu, Haitao, Shi, Yingxiang, Zhang, Shiwen, Tao, Shuang, Wang, Jing, Pang, Siyan, Mao, Huilan, Wang, Wenrui, Yang, Qingling, Chen, Changjie
• Format: Article
• Language: English
• Subjects: CXCL12; Exosomes; Metastasis; miR-372-5p; Polarization; Stemness
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2023.110884

Colorectal cancer (CRC) is the most common malignancy in the digestive system, and tumor metastasis is the main cause of death in clinical patients with CRC. It has been shown that exosomes promote phenotypic changes in macrophages and tumor metastasis in the CRC tumor microenvironment. In this study, we used miRNA-seq technology to screen out the highly expressed miR-372-5p among the miRNAs differentially expressed in plasma exosomes of clinical CRC patients. It was found that miR-372-5p highly expressed in HCT116 exosomes could be phagocytosed by macrophages and promote their polarization into M2 macrophages by regulating the PTEN/AKT pathway. Meanwhile, co-culture of CRC cells with conditioned medium (CM) of macrophages enhanced the EMT, stemness and metastasis of CRC cells. Mechanistically, CRC cells exosome-derived miR-372-5p induced polarized M2 macrophages to secrete chemokine C-X-C-Motif Ligand 12 (CXCL12), which activated the WNT/β-catenin pathway to promote the EMT, stemness and metastatic ability of CRC cells. In summary, this study elucidated the molecular mechanism of exosomal miR-372-5p promoting metastasis and stemness in CRC, which may provide new therapeutic targets for CRC metastasis and prognosis assessment. •MiR-372-5p is highly expressed in the exosomes of colorectal cancer cells.•Exosome-derived miR-372-5p induces polarization of macrophages into M2-macrophages.•Polarized M2-type macrophages promote CXCL12 expression.•CXCL12 activates WNT/β-catenin signaling to promote colorectal cancer progression.•MiR-372-5p plays an oncogene role in the colorectal cancer tumor microenvironment.