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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
miR-1270 suppresses glioblastoma development by transcriptional inhibition of nuclear factor IX
Zhengwei Wang1,2, Jiani Lin3,4, Guisen Tan1,2
1Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin, 541000, Guangxi, China.
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.

