PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4

Wenyong Long, Wei Zhao, Bo Ning, Jing Huang, Junjun Chu, Linfeng Li, Qianquan Ma, Changsheng Xing, Helen Y. Wang, Qing Liu, Rong Fu Wang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of stemness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem cell-like traits. Mechanistically, PHF20 interacts with poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3). Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.

Original languageEnglish (US)
Pages (from-to)147-160
Number of pages14
JournalJournal of molecular cell biology
Volume10
Issue number2
DOIs
StatePublished - Apr 1 2018

    Fingerprint

Keywords

  • PARP1
  • PHF20
  • cancer stem cell-like traits
  • epigenetic regulation
  • neuroblastoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Long, W., Zhao, W., Ning, B., Huang, J., Chu, J., Li, L., Ma, Q., Xing, C., Wang, H. Y., Liu, Q., & Wang, R. F. (2018). PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4. Journal of molecular cell biology, 10(2), 147-160. https://doi.org/10.1093/jmcb/mjy007