Abstract 6589: Exosomal miR-155-5p from early myeloid-derived suppressor cells promotes breast cancer invasion and metastasis by regulating SIRT1

Abstract Early myeloid-derived suppressor cells (eMDSCs) are a heterogeneous group of myeloid cells and have a critical role in the progression of breast cancer. Therefore, exploring the mechanism of communication between eMDSCs and tumor cells is particularly important. In this study, the results showed that eMDSCs co-incubation improved the migration and invasion ability of breast cancer cells by up-regulating the expression of microRNA(miR)-155-5p. Further, we found that eMDSCS-derived exosomes transfer miR-155-5p to breast cancer cells and down-regulate sirtuin 1(SIRT1) expression to promote breast cancer progression. To overcome this challenge, we developed a nanodelivery platform targeting the tumor microenvironment to co-deliver the oligonucleotide inhibitor of miR-155, which demonstrated significant inhibition of tumor growth, migration and invasion in vivo experiments. Overall, our findings suggest that the eMDSCS-derived exosome miR-155-5p promotes invasion and metastasis of breast cancer by targeting SIRT1 and the construction of a tumor microenvironment responsive nanodelivery platform targeting eMDSCs exosome-derived miR-155-5p provides a promising strategy for overcoming breast cancer progression. Citation Format: Guidong Chen, Jinpu Yu. Exosomal miR-155-5p from early myeloid-derived suppressor cells promotes breast cancer invasion and metastasis by regulating SIRT1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6589.