Macrophage-secreted exosomes inhibit breast cancer cell migration via the miR- 101-3p/DLG5 axis

• Published in: Asian Pacific Journal of Tropical Biomedicine
• Main Authors: Yu Liu, Chao-Qun Wang, Yong-Kang Zhu, Jia-Fang Xu, Si-Qi Yin, Qing-Jie Hu, Rui-Qi Yang
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wolters Kluwer Medknow Publications 2023
• Subjects: micro-rna; tumor-associated macrophages; exosomes; breast cancer; dlg5; Arctic medicine. Tropical medicine; RC955-962; Biology (General); QH301-705.5; Arctic
• Online Access: https://doi.org/10.4103/2221-1691.391158; https://doaj.org/article/30f0eeb1a2c84c64a8f83d9423418147

Objective: To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms. Methods: Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis. Differentially expressed miRNAs were identified using RNA sequencing. Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs. The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101. DGL5 expression was detected using qRT-PCR and Western blot analyses. Results: The migration of breast cancer cells was significantly inhibited after addition of exosomes. RNA sequencing results showed that miR-101-3p expression was significantly upregulated. Targetscan analysis predicted that miR-101-3p could target DLG5, and this prediction was verified using the luciferase assay. The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p, and the mRNA and protein levels of DLG5 were suppressed. In contrast, inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5. Furthermore, the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells. Conclusions: Macrophage exosomes can inhibit the migration of breast cancer cells, and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process, which needs further investigation.