N-Glycosylation on Asn50 of SND1 Is Required for Glioma U87 Cell Proliferation and Metastasis.

N-Glycosylation on Asn50 of SND1 Is Required for Glioma U87 Cell Proliferation and Metastasis.
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SND1 Asn50 上的 N-糖基化是胶质瘤 U87 细胞增殖和转移所必需的

DOI:
10.1155/2022/5239006
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发表时间:
2022
影响因子:
4.1
通讯作者:
--
中科院分区:
医学3区
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--
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葡萄球菌含核酸酶结构域蛋白1(Staphylococcal nuclease domain-containing protein 1,SND 1)是一种进化上保守的多结构域蛋白,近年来由于其在多种肿瘤的进展和转移扩散中的正调控作用而受到关注。然而,SND 1糖基化在胶质瘤中的具体作用仍不确定。在本研究中,我们证实了SND 1在人脑胶质瘤中高表达。使用定点突变,我们创建了四个预测的SND 1的N-糖基化位点突变体,并提供了第一个证据表明,SND 1在其Asn 50,Asn 168,Asn 283和Asn 416残基在人脑胶质瘤U87细胞中经历N-糖基化。此外,我们发现去除Asn 50位点上的N-聚糖使SND 1不稳定,并导致其内质网相关降解。此外,失稳的SND 1抑制胶质瘤细胞的增殖和转移。总的来说,我们的研究结果表明,在Asn 50的N-糖基化是必不可少的SND 1的折叠和运输,从而为神经胶质瘤的过程中必不可少的,SND 1作为一个潜在的疾病生物标志物为神经胶质瘤提供了新的见解。
Staphylococcal nuclease domain-containing protein 1 (SND1) is an evolutionarily conserved multidomain protein, which has gained attention recently due to its positive regulation in several cancer progression and metastatic spread. However, the specific contribution of SND1 glycosylation in glioma remains uncertain. In the current study, we confirmed that SND1 was highly expressed in human glioma. Using site-directed mutagenesis, we created four predicted N-glycosylation site mutants for SND1 and provided the first evidence that SND1 undergoes N-glycosylation on its Asn50, Asn168, Asn283, and Asn416 residues in human glioma U87 cells. In addition, we found that removing the N-glycans on the Asn50 site destabilized SND1 and led to its endoplasmic reticulum-associated degradation. Furthermore, destabilized SND1 inhibits the glioma cell proliferation and metastasis. Collectively, our results reveal that N-glycosylation at Asn50 is essential for SND1 folding and trafficking, thus essential for the glioma process, providing new insights for SND1 as a potential disease biomarker for glioma.
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