Effect of the PTPN4/TRAM/TLR4 Signaling Pathway on Angiogenesis Mediated by Rab27a-regulated miR-17-5p Secretion in Breast Cancer Exosomes.

BACKGROUND

The aim of this study was to investigate the mechanisms by which Rab27a regulates the secretion of exosomes in breast cancer to affect angiogenesis and breast cancer (BC) progression.

METHODS

RT‒qPCR was used to detect the levels of Rab27a and miR-17-5p Western blot analysis was used to determine the levels of related proteins. CCK-8, colony formation, EdU staining, and Transwell assays were used to determine cell viability, proliferation and migration. Immunofluorescence was used for detecting the level of angiogenesis-related factors. Angiogenesis assays were used for assessing angiogenesis capacity.

RESULTS

We first observed high expression of Rab27a in breast tissue. Rab27a upregulation promotes cell viability, proliferation, and migration, induces vascular endothelial growth factor A (VEGFA) expression, and enhances angiogenesis. Rab27a upregulates the level of exosomal miR-17-5p Moreover, angiogenesis and BC progression were inhibited after downregulation of miR-17-5p miR-17-5p negatively regulates the expression of PTPN4. The effects of miR-17-5p on cell proliferation and angiogenesis can be reversed to some extent by PTPN4. In addition, miR-17-5p can affect the activity of PTPN4/TRAM/TLR4 pathway by targeting PTPN4.

CONCLUSIONS

In conclusion, our study showed that Rab27a regulates BC exosome miR-17-5p secretion and mediates the PTPN4/TRAM/TLR4 signaling axis to regulate angiogenesis, thereby affecting BC progression.