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

Nat Commun. 2018 Jul 19;9(1):2829. doi: 10.1038/s41467-018-05286-2.

Dan Li ¹, Huajie Song ¹, Hong Mei ¹, Erhu Fang ¹, Xiaojing Wang ¹, Feng Yang ¹, Huanhuan Li ¹, Yajun Chen ², Kai Huang ³, Liduan Zheng ⁴ ⁵, Qiangsong Tong ⁶ ⁷

Affiliations

1 Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China.
2 Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China.
3 Clinical Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China.
4 Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China. ld_zheng@hotmail.com.
5 Clinical Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China. ld_zheng@hotmail.com.
6 Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China. qs_tong@hotmail.com.
7 Clinical Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, P.R. China. qs_tong@hotmail.com.

PMID: 30026490 DOI: 10.1038/s41467-018-05286-2

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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