RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway.
RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway.
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RBM8A 通过 Notch/STAT3 途径促进胶质母细胞瘤生长和侵袭
DOI：
10.3389/fonc.2021.736941
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zou D
中科院分区：
文献类型：
--
作者：
Lin Y;Wei L;Hu B;Zhang J;Wei J;Qian Z;Zou D
背景胶质母细胞瘤（GBM）是一种常见的脑恶性肿瘤，由于其侵袭性生物学行为，预后极差。RNA结合基序蛋白8A（RBM 8A）对多种人类癌症具有不同的作用。然而，RBM 8A在GBM进展中的作用仍不清楚。方法检测94例GBM患者RBM 8A的表达水平，探讨RBM 8A表达与患者预后的相关性。使用体外和体内测定，结合来自癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）的GBM测序数据，我们研究了RBM 8A是否以及如何促进GBM进展。结果RBM 8A在GBM组织中表达上调，且表达水平越高，预后越差。在体外和体内，RBM 8A的敲低抑制GBM进展和侵袭能力。相反，RBM 8A的过表达促进GBM的进展和侵袭能力。GBM数据中差异表达基因的富集分析确定Notch 1/STAT 3网络为RBM 8A的潜在下游靶点，这得到了分子对接研究的支持。此外，我们证明了RBM 8A调节CBF 1的转录活性。γ-分泌酶抑制剂DAPT显著逆转RBM 8A增强的GBM细胞增殖和侵袭，并与下调p-STAT 3和Notch 1蛋白有关。最后，RBM 8A参与Notch 1/STAT 3网络调控的基因的基因集方差分析得分显示出对GBM的良好诊断和预后价值。结论RBM 8A可能通过激活Notch/STAT 3信号通路促进GBM细胞增殖和迁移，提示RBM 8A可能成为治疗GBM的潜在靶点。
Background Glioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear. Methods We investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression. Results RBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM. Conclusions RBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.
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影响因子：
5.5
作者：
Chuang TW;Lee KM;Tarn WY
通讯作者：
Tarn WY
DOI：
10.1007/978-1-4939-7000-1_26
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Burley SK;Berman HM;Kleywegt GJ;Markley JL;Nakamura H;Velankar S
通讯作者：
Velankar S
影响因子：
5.7
作者：
Kim, Tae-Joong;Choi, Jung-Joo;Kim, Byoung-Gie
通讯作者：
Kim, Byoung-Gie
DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Martin, Leenus;Grigoryan, Arsen;Gardner, Lawrence B.
通讯作者：
Gardner, Lawrence B.