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Αλέξανδρος Γ. Σφακιανάκης

Tuesday, February 1, 2022

Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway

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Histol Histopathol. 2022 Feb 1:18425. doi: 10.14670/HH-18-425. Online ahead of print.

ABSTRACT

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.

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 profil es 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.

CONCLUSION: IRAIN repressed glioma dev elopment and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis.

PMID:35102541 | DOI:10.14670/HH-18-425

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