当前位置: X-MOL 学术Cell. Oncol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
QKI deficiency maintains glioma stem cell stemness by activating the SHH/GLI1 signaling pathway.
Cellular Oncology ( IF 6.6 ) Pub Date : 2019-07-10 , DOI: 10.1007/s13402-019-00463-x
Bo Han 1, 2, 3 , Ruijia Wang 1, 3 , Yongjie Chen 1, 3 , Xiangqi Meng 1, 3 , Pengfei Wu 1, 3 , Ziwei Li 1, 3 , Chunbin Duan 1, 3 , Qingbin Li 1, 3 , Yang Li 1, 3 , Shihong Zhao 1, 3 , Chuanlu Jiang 1, 3 , Jinquan Cai 1, 3
Affiliation  

Purpose

Glioblastoma (GBM) stem cells (GSCs) have been found to be the main cause of malignant GBM progression. It has also been found that Quaking homolog (QKI) plays a predominant role in driving GBM development. Here, we aimed to asses the role of QKI in maintaining GSC stemness and inducing the invasiveness of GBM cells.

Methods

Public databases were used to assess the expression of QKI and its correlation with stemness markers in primary GBMs. The CRISPR-Cas9 technology was used to generate QKI knockout GBM cells, and RNA immunoprecipitation was used to assess QKI-GLI1 protein-mRNA interactions. In addition, in vitro and in vivo GBM cell proliferation, migration, xenografting and neurosphere formation assays were performed.

Results

Using public GBM databases, QKI was identified as a potential GSC regulator. We found that QKI could inhibit stem-like cell (SLC) stemness and prolong the survival of xenografted mice. Mechanistically, we found that QKI knockout increased the GLI Family Zinc Finger 1 (GLI1) mRNA level, which is essential for maintaining the self-renewal ability of GSCs. In addition, we found that QKI knockout activated the Hedgehog signaling pathway via Tra-2 and GLI response element (TGE)-specific GLI1 mRNA disruption.

Conclusion

Our data indicate that upregulation of GLI1 induced by QKI deficiency maintains GSC stemness and enhances the invasiveness of GBM cells, thereby hinting at new options for the treatment of GBM.


中文翻译:

QKI 缺乏通过激活 SHH/GLI1 信号通路维持胶质瘤干细胞干细胞。

目的

已发现胶质母细胞瘤 (GBM) 干细胞 (GSC) 是恶性 GBM 进展的主要原因。还发现震颤同系物 (QKI )在推动 GBM 发展中起主要作用。在这里,我们旨在评估 QKI 在维持 GSC 干性和诱导 GBM 细胞侵袭性方面的作用。

方法

公共数据库用于评估 QKI 的表达及其与原发性 GBM 中干性标记的相关性。CRISPR-Cas9技术用于产生QK I敲除GBM细胞,RNA免疫沉淀用于评估QKI - GLI1蛋白-mRNA相互作用。此外,还进行了体外和体内 GBM 细胞增殖、迁移、异种移植和神经球形成试验。

结果

使用公共 GBM 数据库,QKI 被确定为潜在的 GSC 监管机构。我们发现 QKI 可以抑制干细胞样细胞 (SLC) 干性并延长异种移植小鼠的存活时间。从机制上讲,我们发现QKI敲除增加了 GLI 家族锌指 1 ( GLI1 ) mRNA 水平,这对于维持 GSC 的自我更新能力至关重要。此外,我们发现QKI敲除通过 Tra-2 和 GLI 响应元件 (TGE) 特异性GLI1 mRNA 破坏激活了 Hedgehog 信号通路。

结论

我们的数据表明,由 QKI 缺陷诱导的 GLI1 上调维持了 GSC 干性并增强了 GBM 细胞的侵袭性,从而暗示了治疗 GBM 的新选择。
更新日期:2019-07-10
down
wechat
bug