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Author Notes:

Correspondence: shiwang_union@126.com

Author contributions: MH, JH, DL and YYC carried out the molecular genetic studies, animal experiment and participated in the sequence alignment. JRP did the immunohistochemistry. QST, HCJ, STT and SWL performed the statistical analysis. MH, JH and SWL conceived and designed the study and the experimental setup and wrote the manuscript with the help from all coauthors.

All authors read and approved the final manuscript.

Disclosures: The authors declare that they have no competing interests.

Subjects:

Research Funding:

This study was funded by National Natural Science Foundation of China (81372401, 81300409, 81772967).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Transcription factor
  • Transcription regulation
  • Neuroblastoma-prognosis
  • Tumor progression
  • Cancer
  • Expression
  • Gene
  • Pathways
  • Family
  • Kegg

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo

Tools:

Journal Title:

Journal of Experimental & Clinical Cancer Research

Volume:

Volume 39, Number 1

Publisher:

, Pages 52-52

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. Methods: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. Results: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. Conclusions: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.

Copyright information:

© The Author(s). 2020

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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