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Inhibition of H3K9 methyltransferase G9a repressed cell proliferation and induced autophagy in neuroblastoma cells.

Abstract
Histone methylation plays an important role in gene transcription and chromatin organization and is linked to the silencing of a number of critical tumor suppressor genes in tumorigenesis. G9a is a histone methyltransferase (HMTase) for histone H3 lysine 9. In this study, we investigated the role of G9a in neuroblastoma tumor growth together with the G9a inhibitor BIX01294. The exposure of neuroblastoma cells to BIX01294 resulted in the inhibition of cell growth and proliferation, and BIX01294 treatment resulted in the inhibition of the tumorigenicity of neuroblastoma cells in NOD/SCID mice. Therefore, G9a may be a potential therapeutic target in neuroblastoma. Moreover, we found several specific characteristics of autophagy after BIX01294 treatment, including the appearance of membranous vacuoles and microtubule-associated protein light chain 3 (LC3B). Similar results were observed in G9a-knockdown cells. In conclusion, our results demonstrated that G9a is a prognostic marker in neuroblastoma, and revealed a potential role of G9a in regulating the autophagy signaling pathway in neuroblastoma.
AuthorsXiao-Xue Ke, Dunke Zhang, Shunqin Zhu, Qingyou Xia, Zhonghuai Xiang, Hongjuan Cui
JournalPloS one (PLoS One) Vol. 9 Issue 9 Pg. e106962 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID25198515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
Topics
  • Animals
  • Autophagy
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Fluorescent Antibody Technique
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase (antagonists & inhibitors, metabolism)
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neuroblastoma (enzymology, immunology, pathology)

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