Survival Association and Cell Cycle Effects of B7H3 in Neuroblastoma.

Survival Association and Cell Cycle Effects of B7H3 in Neuroblastoma.
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DOI:
10.3340/jkns.2019.0255
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发表时间:
2020-11
影响因子:
1.6
通讯作者:
Hua W
Hua W
中科院分区:
医学4区
文献类型:
--
作者:
Zhang H;Zhang J;Li C;Xu H;Dong R;Chen CC;Hua W

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B7 H3是B7蛋白家族的一员,在神经母细胞瘤(NB)中的功能仍不清楚。在这里,我们研究了B7 H3在临床NB标本中的表达模式,并表征了NB细胞系中B7 H3敲低的表型。 免疫组织化学(IHC)染色,以评估B7 H3在临床NB标本中的表达。使用5个基因表达综合(GEO)数据集(GSE 85047、GSE 45480、GSE 62564、GSE 16476、GSE 49710)分析生存相关性。在B7 H3敲低后进行克隆形成存活和流式细胞术以评估体外细胞增殖和细胞存活。使用SH-SY 5 Y异种移植模型在体内检查B7 H3沉默对NB生长的影响。 免疫组化染色显示,B7 H3在临床NB标本中广泛表达。对5个GEO数据集临床注释的NB标本的转录谱分析显示,B7 H3表达降低与总生存率提高相关。B7 H3基因敲低抑制了SH-SY 5 Y NB模型的体外和体内增殖。细胞周期分析显示,B7 H3沉默可诱导G1/S期阻滞。这种阻滞与E2 F1表达的抑制和Rb表达的诱导有关。 我们的研究结果表明,B7 H3表达与NB患者的临床生存率相关。初步研究表明,B7 H3可能介导G1/S转换。
The function of B7H3, a member of the B7 family of proteins, in neuroblastoma (NB) remains poorly characterized. Here we examine the expression pattern of B7H3 in clinical NB specimens and characterize the phenotype of B7H3 knock-down in NB cell line. Immunohistochemical (IHC) staining was carried out to assess the expression of B7H3 in clinical NB specimens. Survival association was analyzed using five Gene Expression Omnibus (GEO) datasets (GSE85047, GSE45480, GSE62564, GSE16476, GSE49710). Clonogenic survival and flow cytometry were performed after B7H3 knockdown to assess the cellular proliferation and cell survival in vitro. Impact of B7H3 silencing on NB growth was examined in vivo using the SH-SY5Y xenograft model. On IHC staining, B7H3 was widely expressed in clinical NB specimens. Analysis of the transcriptional profiles of five GEO datasets clinically annotated NB specimens revealed that decreased B7H3 expression was associated with improved overall survival. B7H3 knockdown suppressed the proliferation of the SH-SY5Y NB model in vitro and in vivo. Cell cycle analysis revealed that B7H3 silencing induced G1/S arrest. This arrest was associated with the suppression of E2F1 expression and induction of Rb expression. Our results demonstrate that B7H3 expression correlate with clinical survival in NB patients. Preliminary studies suggest that B7H3 may mediate the G1/S transition.
复发的神经母细胞瘤显示出频繁的RAS-MAPK途径突变。
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