miR-1270 suppresses glioblastoma development by transcriptional inhibition of nuclear factor IX.

BACKGROUND: Nuclear factor IX (NFIX) promotes glioblastoma (GBM) development by inducing GBM cell migration and proliferation. However, the upstream regulatory mechanisms of NFIX in GBM remain unclear. METHODS AND RESULTS: To investigate the functional role of miR-1270 in GBM, a stable miR-1270-overexpressing cell model was constructed using lentiviral transduction. The functional consequences were systematically evaluated using Transwell migration, colony formation, and CCK-8 assays, as well as western blotting and quantitative real-time polymerase chain reaction. To validate the therapeutic potential in vivo, we established orthotopic xenograft models in nude mice and longitudinally monitored tumor progression through non-invasive small animal imaging, enabling comprehensive assessment of the antitumor effects of miR-1270 within a physiological microenvironment. A decrease in microRNA-1270 (miR-1270) expression in human GBM samples was observed, which was negatively correlated with NFIX expression. The miR-1270 inhibited NFIX expression, a key driver of GBM cell proliferation and migration. Mechanistic analysis revealed that miR-1270 directly bound to the NFIX promoter region, suppressing its transcriptional activity. The reintroduction of NFIX counteracted the inhibitory effects of miR-1270 on GBM cell malignancy. CONCLUSIONS: This study is the first to report the transcriptional inhibition of NFIX by miR-1270 in GBM cells. These findings suggest that targeting the miR-1270-NFIX axis may provide a promising therapeutic strategy for GBM.