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Cellular Oncology

, Volume 42, Issue 6, pp 801–813 | Cite as

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

  • Bo Han
  • Ruijia Wang
  • Yongjie Chen
  • Xiangqi Meng
  • Pengfei Wu
  • Ziwei Li
  • Chunbin Duan
  • Qingbin Li
  • Yang Li
  • Shihong Zhao
  • Chuanlu JiangEmail author
  • Jinquan CaiEmail author
Original paper

Abstract

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.

Keywords

Glioblastoma QKI Hedgehog signaling pathway GLI1 Glioma stem cells 

Notes

Acknowledgements

This study was supported by the National Key Research and Development Plan (No. 2016YFC0902500), the National Natural Science Foundation of China (No. 81702972, No. 81572701, No. 81772666, and No. 81874204), the China Postdoctoral Science Foundation (2018 M640305), Beijing Postdoctoral Research Foundation (ZZ2019-10)the Chinese Society of Neuro-Oncology, the CACA Foundation (CSNO-2016-MSD12), the Heilongjiang Postdoctoral Science Foundation (LBH-Z18103), the Heilongjiang Health and Family Planning Commission Foundation (2017-201, 2017-068) and the Harbin Medical University Scientific Research Innovation Fund (2017LCZX37, 2017RWZX03, 2017LCZX46, and YJSCX2017-60HYD).

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Tissue specimens were acquired after patient consent and the studiers were approved by the Clinical Research Ethics Committee of the Second Affiliated Hospital of Harbin Medical University.

Supplementary material

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Supplementary Figure S1

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Supplementary Table S3 (XLSX 20 kb)

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Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  • 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
    Email author
  • Jinquan Cai
    • 1
    • 3
    Email author
  1. 1.Department of NeurosurgerySecond Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina
  3. 3.Neuroscience InstituteHeilongjiang Academy of Medical SciencesHarbinChina

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