Background
Increasing studies have found that long noncoding RNAs (lncRNAs) contribute to regulating tumor progression. This study explores the expression characteristics, effects, and related mechanisms of lncRNA IGF1R antisense imprinted non-protein coding RNA (IRAIN) in glioma.
Conclusion
IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis.
Methods
Quantitative real-time PCR (qRT-PCR) was implemented to testify the IRAIN profile in glioma tissues and paracancerous tissues, and the link between the IRAIN level and the clinicopathological indicators of glioma was analyzed. IRAIN overexpression and knockdown cell models were constructed in glioma cells. Cell proliferation was verified by the colony formation experiment, while flow cytometry was implemented to monitor apoptosis. Transwell assay was performed to examine cell invasion and migration. Western blot (WB) was adopted to compare the profiles of the apoptosis-related proteins (Bax, Bcl2, and Caspase3) and IGF-1R-PI3K-NF-κB pathway.
Results
IRAIN was down-regulated in glioma tissues (compared with adjacent normal tissues), and the low IRAIN expression was significantly linked with the larger tumor volume and higher pathological stages. Functionally, overexpressing IRAIN abated glioma cell proliferation, invasion, and migration, promoted apoptosis, and attenuated IGF-1R-PI3K-NF-κB expression and temozolomide (TMZ) resistance, which was also confirmed in the xenograft tumor experiment. The WB result showed that overexpressing IRAIN inactivated the IGF-1R-PI3K-NF-κB pathway. Additionally, the IGF-1R knockdown model was established in U251 cells. Si-IGF-1R induced cell proliferation inhibition, promoted cell death, and reduced cell migration and TMZ resistance, whereas Si-IGF-1R+IRAIN group showed no additional effects on glioma cells compared with the Si-IGF-1R group.