Enhancer of zeste homolog 2 regulates cell differentiation and proliferation in neuroblastoma
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Abstract
BACKGROUND
Neuroblastoma (NB) is one of the most common extracranial solid tumors
occurring in infancy and childhood with highly variable outcomes. Polycomb
group (PcG) proteins are epigenetic gene silencers. Enhancer of zeste homolog
2 (EZH2) is a member of the polycomb repressor complex 2 (PRC2) group,
with the main function to catalyze the polycomb repressor complex by
methylating lysine 9 and 27 of histone H3. This study aimed to investigate the
biological functionality of EZH2 in NB.
METHODS
This was an experimental study with an analysis of correlation initially of the
known prognostic factors of NB patients’ outcomes, by comparing the expression
of v-myc avian myelocytomatosis viral oncogene neuroblastoma (MYCN) with
that of EZH2, on the basis of the patients’ overall and relapse free survival
rates. This was followed with a biological functional study to assess the role of
EZH2 expression in NB.
RESULTS
EZH2 knockdown induces neurite extension and differentiation marker growth
associated protein 43 (GAP43) in NB cells, although it does not affect cell
cycle. By ectopic expression of EZH2, all-trans retinoic acid (ATRA) inducedneurite extension was suppressed and GAP43 was decreased. Overall, EZH2
seems to have an important role in NB cell differentiation. Although EZH2 did
not alter cell proliferation, in the soft agar colony formation assay there was a
significant increase in total colony number and number of large colonies.
CONCLUSION
Our result clarified the potential role of EZH2 in the regulation of cell
differentiation and proliferation, which subsequently may play an important
role in the poor prognosis of NB patients.
Article Details
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Section
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
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References
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