Knockdown of NFE2L3 inhibits the proliferation and radiation resistance of gliomas
Objective To investigate the expression of nuclear factor erythroid-derived 2-like 3(NFE2L3)in gliomas and its effects on the proliferation and radiation resistance of glioma cells,and the underlying mechanism.Methods The mRNA level of NFE2L3 and its prognostic potential in gliomas were analyzed in the Gene Expression Profiling Interactive Analysis(GEPIA)database.Glioma tissue and normal brain tissue from patients admitted to our hospital from January 2013 to December 2017 were collected.Immunohistochemistry was used to detect the protein level of NFE2L3 in glioma tissue,and the correlation between NFE2L3 expression and prognosis of glioma was analyzed.Glioma cells A172 were cultured and transfected with NFE2L3 siRNA.Cell proliferation was detected by cell counting kit-8(CCK-8)assay.Radiotherapy sensitivity was assessed by CCK-8 assay and colony formation assay.Cell cycle distribution was assessed by flow cytometry.Protein levels of CyclinD1 and cyclin-dependent kinase 4 were detected by Western blot.Results GEPIA database analysis showed that compared to normal brain tissue,mRNA level of NFE2L3 significantly increased in glioma tissue,and glioma patients with high mRNA levels of NFE2L3 had poor prognosis.Compared with normal brain tissue,immunohistochemistry showed significantly upregulated NFE2L3 in glioma tissue(P＜0.05).Patients with high expression of NFE2L3 had more advanced World Health Organization(WHO)grading(P＜0.05).Compared with the low NFE2L3 level,glioma patients with high levels of NFE2L3 had a worse prognosis(P＜0.05).Compared with the si-NC group,transfection of si-NFE2L3 in A172 cells significantly downregulated NFE2L3,decreased proliferative rate,increased radiotherapy sensitivity,arrested cell cycle in G0/G1 phase,and downregulated CyclinD1 and CDK4(all P＜0.05).Conclusion NFE2L3 may regulate cell cycle to promote glioma proliferation and resist radiation therapy.
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