Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN

Macrophage-derived exosomes (M phi-Exos) are involved in tumor progression, but its role in glioma is not fully understood. RBP-J is related to macrophage activation. In this study, we assess the role of exosomes derived from RBP-J-overexpressed macrophages (RBP-J OE M phi-Exos) in glioma. The circular RNA (circRNA) profiles in RBP-J OE M phi-Exos and THP-1-like macrophages (WT M phi)-Exos were evaluated using circRNA microarray. Then the functions of M phi-Exo-circRNA in glioma cells were assessed via CCK-8, EdU, Transwell invasion, and nude mouse assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson's correlation analysis were adopted to confirm interactions. We found that circRNA BTG (circBTG2) is upregulated in RBP-J OE M phi-Exos compared to WT M phi-Exos. RBP-J OE M phi-Exos co-culture and circBTG2 overexpression inhibited proliferation and invasion of glioma cells, whereas circBTG2 knockdown promotes tumor growth in vivo. The effects of RBP-J OE M phi-Exos on glioma cells can be reversed by the circBTG2 knockdown. In conclusions, Exo-circBTG2 secreted from RBP-J OE M phi inhibits tumor progression through the circBTG2/miR-25-3p/PTEN pathway, and circBTG2 is probably a diagnostic biomarker and potential target for glioma therapy.

Automated summary

This study reveals that exosomes derived from RBP-J-overexpressed macrophages inhibit tumor progression in glioma cells through the circBTG2/miR-25-3p/PTEN pathway, suggesting circBTG2 as a potential diagnostic biomarker and therapeutic target for glioma.