Bone Marrow Mesenchymal Stem Cells Restrain the Migration and Invasion of Breast Cancer Cells by Up-Regulating miR-2158 and Inactivating RAI2/NLRP3 Pathway

Abstract

Exosomes are the key mediator for intercellular communication and participate in malignancies. Short non-coding RNAs derived from BMSCs-originated exosomes (BMSCs-exosomes) can be employed as biomolecules for tumor treatment. Here to we aim to dissect the function of microRNA-2158 from BMSCs-exosomes in breast malignant disease. Breast malignant cells received a separated transfection of miR-2158-mimics and miR-2158-inhibitor, and also treated with BMSCoriginated exosomes followed by analysis of cell viability by MTT method, cell invading and migrating capabilities via Transwell assays and protein levels of EMT-related and RAI2/NLRP3-related proteins by Western-blot. Breast cancer cells exhibited a significantly enhanced miR-2158 expression after transfection with miR-2158-mimics or treatment with BMSC-EXO, while it was reduced by miR-2158-inhibitor. As the miR-2158 was up-regulated, a significant impediment of proliferation and migration was denoted, along with a down-regulation of RAI2/NLRP3 signal transduction pathway and a retarded EMT process. Furthermore, cell proliferating and migrating capabilities were strengthened by miR-2158-inhibitor, together with an enhanced RAI2/NLRP3 signal and a strengthened EMT process. In conclusion, miR-2158 retarded the in vitro proliferating and migrating activities of breast malignant cells, leading to the inactivation of RAI2/NLRP3 signal transduction pathway, thereby exerting its tumor-suppressing function.