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.

Comprehensive evaluation of differential long non‑coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra

“…Randall et al (52) reported that activation of FZD7, Of the genes identified in the present study that were consistent with those in the literature, only four miRNAs with MREs within ITGB8 were associated with cartilage degeneration and calcification, including miR-20a-5p, miR-145-5p, miR-93-5p and miR-17-5p. Guo et al (25) reported that miR-20a-5p in exosomes from breast cancer cells promoted the proliferation and differentiation of osteoclasts. Furthermore, Chen et al (53) revealed that decreased miR-145-5p expression promoted the proliferation of osteoclasts to aggravate cartilage erosion by targeting OPG.…”

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

“…In addition, tumor cells have been shown to increase the number and activity of other cells. Breast cancer cell-derived exosomes can promote the proliferation and differentiation of osteoclasts through miRNA-20a-5p (Guo et al, 2019), and prostate cancer cell-derived exosomes exhibit strong promotion of osteoclastogenesis in vitro (Inder et al, 2014). This may contribute to the inherent mechanism through which patients with tumors exhibit osteoporosis.…”

MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages

“…In addition, uptake of EVs enriched with miR-145 derived from colorectal cancer cells by macrophages increases their oncogenic effects via downregulation of histone deacetylase 11 (HDAC11) [ 79 ]. Guo et al found that exosomal transfer of miR-20a-5p released from breast cancer cells facilitate breast cancer development and metastasis [ 149 ]. They demonstrated that exosomal transfer of miR-20a-5p promotes migration of breast tumor cells to bone [ 149 ].…”

“…Guo et al found that exosomal transfer of miR-20a-5p released from breast cancer cells facilitate breast cancer development and metastasis [ 149 ]. They demonstrated that exosomal transfer of miR-20a-5p promotes migration of breast tumor cells to bone [ 149 ]. In another study performed on breast cancer cells depicts that transfer of extracellular miR-375 from tumor cells to TAMs induced their migration and infiltration [ 71 ].…”