Exosome miR‐134‐5p restrains breast cancer progression via regulating PI3K/AKT pathway by targeting ARHGAP1

Abstract Aim Exosomes has been shown to be involved in the regulation of cancer progression. However, the role of exosome miR‐134‐5p in breast cancer (BC) progression is unclear. Methods Exosomes were extracted from BC cells (MCF‐7 and MDA‐MB‐231) using differential centrifugation and were observed by transmission electron microscope (TEM). The protein levels of exosome markers, apoptosis markers, Rho GTPase activating protein 1 (ARHGAP1, an important oncogene in BC) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) markers were detected by western blot (WB) assay. Quantitative real‐time PCR was used to measure the expression levels of miR‐134‐5p and ARHGAP1. Cell cycle and apoptosis, colony number, viability, migration, and invasion were determined by flow cytometry, colony formation assay, MTT assay, and transwell assay, respectively. The interaction between miR‐134‐5p and ARHGAP1 was confirmed using a dual‐luciferase reporter assay. Xenograft models were constructed to verify the role of exosome miR‐134‐5p in BC tumor growth in vivo. Results MiR‐134‐5p was lowly expressed in BC cells and in the exosomes of BC cells. Overexpressed exosome miR‐134‐5p suppressed the proliferation, migration, invasion, and promoted the apoptosis of BC cells. ARHGAP1 was a target of miR‐134‐5p, and its silencing could inhibit BC progression. In addition, ARHGAP1 overexpression could reverse the negative regulation of miR‐134‐5p on BC progression. MiR‐134‐5p could target ARHGAP1 to inhibit the activity of PI3K/AKT pathway. Exosome miR‐134‐5p overexpression could suppress BC tumor growth via targeting ARHGAP1 in vivo. Conclusion Exosome miR‐134‐5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR‐134‐5p might be a therapeutic target for BC.