QKI deficiency maintains glioma stem cell stemness by activating the SHH/GLI1 signaling pathway

被引：19

作者：

Han, Bo ^{[1
,2
,3
]}

Wang, Ruijia ^{[1
,3
]}

Chen, Yongjie ^{[1
,3
]}

Meng, Xiangqi ^{[1
,3
]}

Wu, Pengfei ^{[1
,3
]}

Li, Ziwei ^{[1
,3
]}

Duan, Chunbin ^{[1
,3
]}

Li, Qingbin ^{[1
,3
]}

Li, Yang ^{[1
,3
]}

Zhao, Shihong ^{[1
,3
]}

Jiang, Chuanlu ^{[1
,3
]}

Cai, Jinquan ^{[1
,3
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 2, Dept Neurosurg, Harbin 150086, Peoples R China

[2] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China

[3] Heilongjiang Acad Med Sci, Neurosci Inst, Harbin 150086, Peoples R China

来源：

CELLULAR ONCOLOGY | 2019年 / 42卷 / 06期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Glioblastoma; QKI; Hedgehog signaling pathway; GLI1; Glioma stem cells; RNA-BINDING PROTEINS; EMBRYONIC STEM; GLIOBLASTOMA; CANCER; STAR; EXPRESSION; TEMOZOLOMIDE; INVASION; GROWTH; DIFFERENTIATION;

D O I：

10.1007/s13402-019-00463-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 GBMcells, and RNA immunoprecipitation was used to assess QKI-GLI1 protein-mRNA interactions. In addition, in vitro and in vivo GBMcell 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.

引用

页码：801 / 813

页数：13

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