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.Copyright © 2023. Published by Elsevier Inc.
REFERENCES & ADDITIONAL READING
Xiuru Shi,Ke Wei,Yulun Wu,Lingyu Mao,Wenhao Pei,Haitao Zhu,Yinxiang Shi,Shiwen Zhang,Shuang Tao,Jing Wang,Siyan Pang,Huilan Mao,Wenrui Wang,Qingling Yang,Changjie Chen
Xiuru Shi
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Ke Wei
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Yulun Wu
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Lingyu Mao
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Wenhao Pei
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Haitao Zhu
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Yinxiang Shi
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Shiwen Zhang
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Shuang Tao
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Jing Wang
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Siyan Pang
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Huilan Mao
Anhui Province Key Laboratory of Translational Cancer Research (Bengbu Medical College), Anhui 233030, China.
Wenrui Wang
Department of Biotechnology, Bengbu Medical College, Anhui 233030, China. Electronic address: wenrui-wang1983@163.com.
Qingling Yang
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China. Electronic address: yqlmimi@163.com.
Changjie Chen
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China. Electronic address: tochenchangjie@163.com.
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