Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma
via repressing IGF-1R-PI3K-NF-κB signaling pathway
Aishun Guo1, Guixia Fang2, Zhenrong Lin1, Shuishun Zheng1, Zhijun Zhuang1, Ruisheng Lin1 and Yanling Lin3
1Department of Neurosurgery, 2Department of Nephrology and 3Department of Pathology, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China
Corresponding Author: Yanling Lin, Department of Pathology, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59 West Shengli Road, Zhangzhou 363000, Fujian Province, China. e-mail: lyl_fj@163.com
Summary. 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 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.
Conclusion. IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis. Histol Histopathol 37, 543-554 (2022)
Key words: Glioma, IRAIN, Signaling pathway, Temozolomide, Resistance
DOI: 10.14670/HH-18-425
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©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
