Decrease of circARID1A retards glioblastoma invasion by modulating miR-370-3p/ TGFBR2 pathway.

Abstract

Increasing evidence suggests that circular RNAs (circRNAs) are involved in regulating tumor biological activity. Glioblastoma (GBM) is one of the most lethal diseases characterized by highly aggressive proliferative and invasive behaviors. We aimed to explore how circRNAs influenced GBM biological activity. By circRNA array analysis we found that circARID1A was significantly up-regulated in GBM. Next, we found that circARID1A was up-regulated in GBM tissues and cell lines. Interfering with circARID1A inhibited the migration and invasion of a human GBM cell line U87. By performing dual-luciferase reporter assays, RNA pull-down and fluorescent in situ hybridization (FISH), we determined that circARID1A directly bound to miR-370-3p. Moreover, we confirmed that transforming growth factor beta receptor 2 (TGFBR2) was the target gene of miR-370-3p by performing RNA pull-down, dual-luciferase reporter assays and western blotting. Further experiments verified that circARID1A promoted GBM cell migration and invasion by modulating miR-370-3p/ TGFBR2 pathway. In addition, we demonstrated that silencing circARID1A restrain the growth of GBM in vivo. Finally, we showed that circARID1A was abundant in GBM cell derived exosomes. In conclusion, circARID1A participated in regulating migration and invasion of GBM via modulation of miR-370-3p/ TGFBR2 and thus may be a potential serum biomarker of GBM.