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.
[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Pediat Surg, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China.
[2]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pathol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China.
[3]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Genom Res, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China.
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