HOXC9 links cell-cycle exit and neuronal differentiation and is a prognostic marker in neuroblastoma

Ling Mao, Jane Ding, Yunhong Zha, Liqun Yang, Brian A. McCarthy, William King, Hongjuan Cui, Hanfei Ding

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Differentiation status in neuroblastoma strongly affects clinical outcomes and inducing differentiation is a treatment strategy in this disease. However, the molecular mechanisms that control neuroblastoma differentiation are not well understood. Here, we show that high-level HOXC9 expression is associated with neuroblastoma differentiation and is prognostic for better survival in neuroblastoma patients. HOXC9 induces growth arrest and neuronal differentiation in neuroblastoma cells by directly targeting both cell-cycle - promoting and neuronal differentiation genes. HOXC9 expression is upregulated by retinoic acid (RA), and knockdown of HOXC9 expression confers resistance to RA-induced growth arrest and differentiation. Moreover, HOXC9 expression is epigenetically silenced in RA-resistant neuroblastoma cells, and forced HOXC9 expression is sufficient to inhibit their proliferation and tumorigenecity. These findings identified HOXC9 as a key regulator of neuroblastoma differentiation and suggested a therapeutic strategy for RA-resistant neuroblastomas through epigenetic activation of HOXC9 expression.

Original languageEnglish (US)
Pages (from-to)4314-4324
Number of pages11
JournalCancer Research
Volume71
Issue number12
DOIs
StatePublished - Jun 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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