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

Nature Communications
Dan LiQiangsong Tong

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.

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Citations

Jun 22, 2020·Clinical and Translational Medicine·Jing YeFeng Zhang
Mar 29, 2020·Journal of Hematology & Oncology·Huajie SongQiangsong Tong
Aug 13, 2020·Journal of Cellular Physiology·Wen GengAiyuan Wang
Jan 20, 2019·Toxins·Timothy Patrick JenkinsAndreas Hougaard Laustsen
Feb 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Keisuke ShimadaMasahito Ikawa
Feb 20, 2021·Stem Cell Reports·Yikai HuangJinzhong Qin
Jan 27, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiang ZhaoQiangsong Tong
Nov 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yanan LiZi Wang

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Datasets Mentioned

BETA
GSE14340
GSE16476
GSE62564
U133
GSE107516
GSE21032
EGAD00001000282

Methods Mentioned

BETA
transfection
xenografts
co-immunoprecipitation
RNA-seq
immunoprecipitation
PCR
ChIP
pull-down
transgenic
electrophoresis

Software Mentioned

ProteinPilot
Peptiderive
HTSeq
GSEA

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