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
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Department of Biotechnology, Bengbu Medical College, Anhui 233030, China.
Cell Signal. 2023 Nov;111:110884. doi: 10.1016/j.cellsig.2023.110884. Epub 2023 Sep 9.
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.
结直肠癌（CRC）是消化系统中最常见的恶性肿瘤，肿瘤转移是CRC临床患者死亡的主要原因。研究表明，外泌体可促进CRC肿瘤微环境中巨噬细胞的表型变化和肿瘤转移。在本研究中，我们使用miRNA测序技术从临床CRC患者血浆外泌体中差异表达的miRNA中筛选出高表达的miR-372-5p。研究发现，HCT116外泌体中高表达的miR-372-5p可被巨噬细胞吞噬，并通过调节PTEN/AKT途径促进其极化为M2巨噬细胞。同时，CRC细胞与巨噬细胞条件培养基（CM）共培养可增强CRC细胞的上皮-间质转化（EMT）、干性和转移能力。机制上，CRC细胞来源的外泌体miR-372-5p诱导极化的M2巨噬细胞分泌趋化因子C-X-C基序配体12（CXCL12），激活WNT/β-连环蛋白途径，促进CRC细胞的EMT、干性和转移能力。总之，本研究阐明了外泌体miR-372-5p促进CRC转移和干性的分子机制，这可能为CRC转移和预后评估提供新的治疗靶点。
