AdipoR1-mediated miR-3908 inhibits glioblastoma tumorigenicity through downregulation of STAT2 associated with the AMPK/SIRT1 pathway.

A prospective method of treatment for cancer is to inhibit oncogene signaling pathways with microRNA (miRNA or miR). In the present study, whether the expression of STAT2, AdipoR1/AMPK/SIRT1 pathway of glioma is regulated by miR-3908 was explored. To confirm whether the predicted miR-3908 is matched with STAT2 and AdipoR1, 3'UTR luciferase activity of STAT2 and AdipoR1 was assessed. In the presence of the mimics or inhibitors of miR-3908, cell function of glioma cells, such as proliferation, growth, migration, invasion and apoptosis were analyzed. The expression of AdipoR1 and its downstream AMPK/SIRT1 pathway proteins or STAT2 were examined. Luciferase reporter analysis showed that miR-3908 directly target STAT2 and AdipoR1. miR-3908 suppressed expression of STAT2 or AdipoR1 and downregulated AdipoR1 pathway genes, including AMPK, p-AMPK and SIRT1. miR-3908 inhibited tumorigenicity, migration, growth and invasion in glioma cell lines U251 and U87 as well as increased apoptosis of these cells. The pathways related to tumorigenicity and tumor progression, STAT2 and AdipoR1/AMPK/SIRT1 could be restrained by miR-3908. In conclusion, restoration of miR-3908 expression induced suppression of cancer progression and glioblastoma tumorigenicity. The present study discovered novel tumorigenesis associated with miR-3908, which may represent a new target in treatment for glioblastoma.