Exosomal microRNA-143-3P and its effect on biological behavior and angiogenesis in breast cancer

We undertook this study to investigate the effect of exosomal microRNA-143-3p (miR-143-3p) on the biological behavior and angiogenesis in breast cancer. We transfected human breast cancer cells (MDA-MB-231) with miR-143-3p Agomir or Agomir-NC, and we isolated the exosomes (ex) that were secreted and named these miR-143-3p Agomir-ex and Agomir-NC-ex, respectively. We performed real-time polymerase chain reaction (real-time PCR) to detect the level of exosomal miR-143-3p. We treated the MDA-MB-231 cells with exosomal miR-143-3p Agomir-ex and Agomir-NC-ex. We measured the cellular miR-143-3p concentration using real-time PCR, cell proliferation using the cell counting kit-8 (CCK-8), apoptosis using flow cytometry, the abilities of cell migration and invasion using FCM (flow cytometry), and the levels of vascular endothelial growth factor (VEGF) in cell supernatants using the enzyme-linked immunosorbent assay (ELISA). We constructed nude mouse MDA-MB-231 cell transplantation tumor models and injected Agomir-NC, miR-143-3p Agomir, Agomir-NC-ex, and miR-143-3p Agomir-ex intratumorally to observe the tumor growth. Next, we isolated the tumor tissues and measured the expression of miR-143-3p, pathological change, apoptosis, levels of Ki67, VEGF, and CD31, and microvessel density using real-time PCR, hematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemistry, respectively. We found that, in comparison with Agomir-NC-ex, the expression of miR-143-3p was upregulated in miR-143-3p Agomir-ex, and miR-143-3p Agomir-ex increased the levels of miR-143-3p in breast cancer cells, inhibited the proliferation, migration, and invasion of breast cancer cells, promoted apoptosis, and decreased the levels of VEGF in the cell supernatant. Our experiments with the nude mouse transplantation tumor revealed that both miR-143-3p Agomir-ex and miR-143-3p Agomir reduced tumor growth and the expression of Ki67 protein, increased the levels of miR-143-3p, promoted tumor cell apoptosis, and inhibited the expressions of CD31 protein and VEGF, and angiogenesis. In our current study, we found that the exosomal miR-143-3p inhibited malignant biological behavior and angiogenesis in breast cancer.