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Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4.

Abstract：

:Recent studies suggest the emerging roles of armadillo (ARM) family proteins in tumor progression. However, the functions and underlying mechanisms of ARM members in tumorigenesis and aggressiveness of neuroblastoma (NB) remain to be determined. Herein, we identify armadillo repeat containing 12 (ARMC12) as an ARM member associated with NB progression. ARMC12 promotes the growth and aggressiveness of NB cell lines. Mechanistically, ARMC12 physically interacts with retinoblastoma binding protein 4 (RBBP4) to facilitate the formation and activity of polycomb repressive complex 2, resulting in transcriptional repression of tumor suppressive genes. Blocking the interaction between ARMC12 and RBBP4 by cell-penetrating inhibitory peptide activates the downstream gene expression and suppresses the tumorigenesis and aggressiveness of NB cells. Both ARMC12 and RBBP4 are upregulated in NB tissues, and are associated with unfavorable outcome of patients. These findings suggest the crucial roles of ARMC12 in tumor progression and a potential therapeutic approach for NB.

journal_name

Nat Commun

journal_title

Nature communications

authors

Li D,Song H,Mei H,Fang E,Wang X,Yang F,Li H,Chen Y,Huang K,Zheng L,Tong Q

doi

10.1038/s41467-018-05286-2

subject

Has Abstract

pub_date

2018-07-19 00:00:00

pages

2829

issue

1

issn

2041-1723

pii

10.1038/s41467-018-05286-2

journal_volume

9

pub_type

杂志文章

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