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Enhancer of zeste homolog 2 regulates cell differentiation and proliferation in neuroblastoma (Enhancer of zeste homolog 2 berperan pada diferensiasi dan proliferasi sel 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 143. This study aimed to i nvestigate 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 patient & 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 EZ142, all-trans retinoic acid (ATRA) induced neurite extension was suppressed and GAP43 was decreased. Overall; EZH2 seems to have an important role in NB cell differentiation. Although EZI12 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 EZI-12 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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UNIVERSITAS MEDICINA, 33 (3) 2014 : 154-162

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Jakarta : UNIVERSA MEDICINA/FK UNIVERSITAS TRISAKTI., 2014

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9p

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1907-3062

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