High-Metastatic Triple-Negative Breast Cancers Cell-Derived Exosomal miR-525-5p Inhibits Anoikis and Promotes Metastasis of Low-Metastatic TNBC Cells via Downregulating Bax

Abstract

Background: Exosomes play crucial roles in cell-to-cell communication and metastatic progression in triple-negative breast cancers (TNBC). However, the intercellular communication between different metastatic potential cancer cells is not fully understood in TNBC. Thus, we aimed to evaluate miR-525-5p mechanism in the communication between different metastatic potential TNBC cells. Methods: Exosomes were collected from high-metastatic (HM)- and low-metastatic (LM)-TNBC cells and then identified by nanoparticle tracking analysis (NTA) and transmission electronic microscopy (TEM), and miR-525-5p level was evaluated by real-time quantitative-polymerase chain reaction (RT-qPCR). Additionally, in vitro assays were used to clarify the role of exosomal miR-525-5p to regulate the crosstalk between HM- and LM-TNBC cells. Moreover, dual-luciferase reporter assay was used to identify the relationship between miR-525-5p and its target gene Bcl-2 associated X (Bax). Western blot assay was performed to determine Bax, Bcl-2 and cleaved caspase 3 levels in TNBC cells. Results: MiR-525-5p level in HM-TNBC cells exosomes significantly increased compared to LM-TNBC cells exosomes. Additionally, HM-TNBC cells exosomes can deliver miR-525-5p to LM-TNBC cells. Moreover, exosomal miR-525-5p derived from HM-TNBC cells enhanced the migration of LM-TNBC cells. Furthermore, Bax was found as a potential target of miR-525-5p. Exosomal miR-525-5p inhibited anoikis of recipient cancer cells via downregulation of Bax and cleaved caspase 3 and upregula-tion of Bcl-2. Conclusions: Our results show that exosomal miR-525-5p could suppress anoikis and facilitate LM-TNBC cells metastasis via Bax downregulation.