Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1

Abstract

Bone metastasis of breast cancer makes patients suffer from pain, fractures, spinal cord compression, and hypercalcemia, and is almost incurable. Although the mechanisms of bone metastasis in breast cancers have been studied intensively, novel specific target will be helpful to the development of new therapeutic strategy of breast cancer. Herein, we focused on the microRNA of tumor cell-derived exosomes to investigate the communication between the bone microenvironment and tumor cells. The expression of miR-20a-5p in the primary murine bone marrow macrophages (BMMs), MCF-10A, MCF-7, and MDA-MB-231 cell lines, as well as the cell-derived exosomes were assessed by qRT-PCR. Transwell assays were used to evaluate the effects of miR-20a-5p on tumor cell migration and invasion. The expression of exosomes marker including CD63and TSG101 was detected by Western Blot. Cell cycle distribution of BMMs was analyzed by flow cytometry. 3-UTR luciferase reporter assays were used to validate the putative binding between miR-20a-5p and SRCIN1. MiR-20a-5p was highly expressed in breast tumor tissues and the exosomes of MDA-MB-231 cells. MiR-20a-5p promoted migration and invasion in MDA-MB-231 cells, and the proliferation and differentiation of osteoclasts. MDA-MB-231 cell-derived exosomes transferred miR-20a-5p to BMMs and facilitated the osteoclastogenesis via targeting SRCIN1. The present work provides evidence that miR-20a-5p transferred from breast cancer cell-derived exosomes promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1, providing scientific foundations for the development of exosome or miR-20a-5p targeted therapeutic intervention in breast cancer progression.

Keywords: SRCIN1; bone metastasis; breast cancer; exosomes; miR-20a-5p.