Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.
Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.
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胶质瘤中 CAPON 的低表达通过 Akt 信号通路促进细胞增殖
DOI：
10.3390/ijms17111859
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发表时间：
2016-11-18
影响因子：
5.6
通讯作者：
Yu R
中科院分区：
文献类型：
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作者：
Gao S;Wang J;Zhang T;Liu G;Jin L;Ji D;Wang P;Meng Q;Zhu Y;Yu R
CAPON是一氧化氮合酶1（NOS 1）的衔接蛋白。CAPON在人脑中有两种亚型：CAPON-L（CAPON的长型）和CAPON-S（CAPON的短型）。最近的研究表明，CAPON参与肿瘤发生超出其经典的作用，在NOS 1活性调节。在本研究中，我们发现CAPON-S的蛋白水平在胶质瘤组织中显著降低，但不低于CAPON-L。因此，我们建立了慢病毒介导的CAPON-S过表达或下调的稳定细胞系，并通过CCK 8、EdU和流式细胞术检测来研究CAPON-S在胶质瘤细胞增殖中的作用。CAPON-S的过表达降低了胶质瘤细胞的细胞变异性和EdU阳性细胞的百分比，并将细胞阻滞在G1期。短发夹RNA沉默CAPON则表现出相反的效果。细胞内信号阵列显示CAPON-S过表达可显著降低胶质瘤细胞中Akt和S6核糖体蛋白的磷酸化水平，Western blot进一步证实了这一点。这些发现表明CAPON可能在人脑胶质瘤中起肿瘤抑制剂的作用，并且CAPON-S过表达引起的Akt信号通路的失活可能为CAPON在胶质瘤细胞增殖中的潜在机制提供见解。
CAPON is an adapter protein for nitric oxide synthase 1 (NOS1). CAPON has two isoforms in the human brain: CAPON-L (long form of CAPON) and CAPON-S (short form of CAPON). Recent studies have indicated the involvement of CAPON in tumorigenesis beyond its classical role in NOS1 activity regulation. In this study, we found that the protein levels of CAPON-S, but not than CAPON-L, were significantly decreased in glioma tissues. Therefore, we established lentivirus-mediated stable cell lines with CAPON-S overexpression or down-regulation, and investigated the role of CAPON-S in the proliferation of glioma cells by using CCK8, EdU, and flow cytometry assays. Overexpression of CAPON-S reduced the cell variability and the percentage of EdU-positive cells, and arrested the cells in the G1 phase in glioma cells. Silencing of CAPON by short-hairpin RNA showed the opposite effects. Furthermore, an intracellular signaling array revealed that overexpression of CAPON-S resulted in a remarkable reduction in the phosphorylation of Akt and S6 ribosomal protein in glioma cells, which was further confirmed by Western blot. These findings suggest that CAPON may function as a tumor suppressor in human brain glioma and that the inactivation of the Akt signaling pathway caused by CAPON-S overexpression may provide insight into the underlying mechanism of CAPON in glioma cell proliferation.
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影响因子：
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作者：
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