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Enhancer of zeste homolog 2 regulates cell differentiation and proliferation in neuroblastoma

Amallia N. Setyawati, Takehiko Kamijo
Submission date: Monday, 30 November 2015
Published date: Tuesday, 02 December 2014
DOI: http://dx.doi.org/10.18051/UnivMed.2014.v33.153-162

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.


Keywords


Neuroblastoma; EZH2; MYCN

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