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Homeobox B8 Targets Sterile Alpha Motif Domain-Containing Protein 9 and Drives Glioma Progression

  • Wenping Ma
  • Hongze Jin
  • Wenjie Liu
  • Xiaojuan Li
  • Xingang Zhou
  • Xinwu Guo
  • Runfa Tian
  • Qi Cui
  • Junjie Luo
  • Yueying Jiao
  • Youtao YuEmail author
  • Haifeng YangEmail author
  • Hongshan ZhaoEmail author
Original Article

Abstract

Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8 (HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.

Keywords

HOXB8 Glioma Aggressiveness SAMD9 Treatment 

Notes

Acknowledgements

We would like to give special thanks to Dr. Wangshu Xu for her helpful editing improvements and Dr. Hongqiang Du for his contributions to trial management. This work was supported by the National Natural Science Foundation of China (31571298).

Conflict of interest

The authors declare no competing interests.

Supplementary material

12264_2019_436_MOESM1_ESM.pdf (1.9 mb)
Supplementary material 1 (PDF 1980 kb)

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Wenping Ma
    • 1
    • 2
    • 3
  • Hongze Jin
    • 4
  • Wenjie Liu
    • 5
  • Xiaojuan Li
    • 6
  • Xingang Zhou
    • 7
  • Xinwu Guo
    • 8
  • Runfa Tian
    • 2
  • Qi Cui
    • 1
  • Junjie Luo
    • 1
  • Yueying Jiao
    • 1
  • Youtao Yu
    • 9
    Email author
  • Haifeng Yang
    • 10
    Email author
  • Hongshan Zhao
    • 1
    Email author
  1. 1.Department of Medical Genetics, School of Basic Medical SciencesPeking University Health Science CenterBeijingChina
  2. 2.Department of Neurosurgery, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  3. 3.Beijing Neurosurgical InstituteBeijingChina
  4. 4.The Second Affiliated Hospital of Zhejiang University School of MedicineChangxingChina
  5. 5.Department of Hepatobiliary Surgery, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  6. 6.Department of RadiologyThe First Hospital of Harbin Medical UniversityHarbinChina
  7. 7.Department of PathologyBeijing Ditan Hospital, Capital Medical UniversityBeijingChina
  8. 8.Sansure Biotech Inc.ChangshaChina
  9. 9.Department of Intervention TherapyThe Fourth Medical Center of PLA General HospitalBeijingChina
  10. 10.Department of NeurosurgerySanbo Brain Hospital, Capital Medical UniversityBeijingChina

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