Silvestrol alleviates glioblastoma progression through ERK pathway modulation and MANBA and NRG-1 expression
作者机构：Neurosurgery DepartmentThe First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina Neurosurgery DepartmentChangdu People’s Hospital of TibetChangduChina
出 版 物：《BIOCELL》 (生物细胞（英文）)
年 卷 期：2024年第48卷第7期
页 面：1081-1093页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Glioblastoma Silvestrol ERK pathway MANBA NRG-1
摘 要：Background:Glioblastoma,a notably malignant tumor within the central nervous system,is distinguished by its aggressive ***,a robust inhibitor of the RNA helicase eukaryotic initiation factor 4A(eIF4A),has shown significant potential as an anticancer ***,the impact of silvestrol on glioblastoma,especially its molecular mechanisms,has not been fully ***:This investigation employed a variety of in vitro assays,such as cell counting kit-8(CCK-8),clonogenic,5-ethynyl-2′-deoxyuridine(EDU),wound healing,and flow cytometry,to evaluate cell cycle progression,apoptosis,cell viability,and *** blot analysis was also performed to study the apoptosis and extracellular regulated kinase(ERK)*** the ERK pathway was inhibited,differentially expressed genes(DEGs)in U87 cells were identified,followed by an analysis of target genes using the gene expression profiling interactive analysis(GEPIA)***:Silvestrol significantly suppressed the proliferation,migration,and colony formation of glioma *** caused cell cycle arrest and enhanced apoptosis in these ***,silvestrol stimulated the ERK pathway,with these effects being reversible by an ERK phosphorylation *** combined with GEPIA,GSCA,UALCAN,TIMER database screened 4 potential drug targets of silvestrol:chromosome 1 open reading frame 226(C1ORF226),mannosidase beta A(MANBA),IQ motif and Sec7 domain 2(IQSEC2),neuregulin 1(NRG-1).Among them,C1ORF226 was lower risk gene while MANBA,IQSEC2,and NRG-1 were high-risk ***,silvestrol notably reduced MANBA mRNA levels,which could be reversed by inhibiting ERK ***,silvestrol markedly decreased NRG-1 protein levels,with an additional reduction observed when the ERK pathway was ***:Silvestrol’s anti-glioma effects are primarily due to the suppression of MANBA expression via the ERK pathway and possibly by hindering the translation of N
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