Published in Nature Communications

Armadillo Repeat Containing 12 Promotes Neuroblastoma Progression Through Interaction with Retinoblastoma Binding 4

Background

Armadillo (ARM) family play an important role in tumor progression. This paper identified ARMC12 as an ARM member associated with neuroblastoma progression.

1 Materials 6 · Tumor cells (1×10 )

2 RNA Isolation · Total RNA extracted using TRIzol® Research Pipeline 3 Library Construction · mRNA libraries for RNA-seq

4 Sequencing · Illumina platform

5 Bioinformatic Analysis · Differential expression · GSEA ( Set Enrichment Analysis)

Research Results

Armadillo repeat containing 12 (ARMC12 ), an ARM member associated with NB progression, 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 (PRC2), resulting in transcriptional repression of tumor suppressive .

Blocking the interaction between ARMC12 and RBBP4 by cell-penetrating inhibitory peptide activates 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 outcomes for patients. Analysis Showcase

Novogene’s RNA-seq analysis helped to screen differentially expressed genes upon ARMC12 overexpression. Five genes, CADM1 , EGLN3 , HRK , HS6ST3 , and SMAD9 , were identified and further proved to be suppressed by ARMC12 , facilitating the growth and aggressiveness of NB cells.

a k Moc ARMC12 100 Correlated genes Correlated genes HS6ST2 (GSE16476) (GSE62564) Down: Up: 327 3798 HS6ST3 CADM1 3224 2901 443 82 0 SMAD9 RNA-Seq ChIP-X EGLN3 105 MBNL3

(padj) 0 50 4493 0 10 HRK CHPT1 –1.04 852 14 0 MYO1B –0.69 –Log SETD7 –0.35 PPP1R3C 0.00 155 4 PLS1 0.35 0.69 1.3 TMEM45B 420 SLC7A11 1.04 0 4 8 –8 –4 12 16 –16 –12

Log2 (fold change)

Volcano plots (left panel), Venn diagram (middle panel), and heatmap (right panel) show the alteration of gene expression in ARMC12 overexpressed or normal expressed cells. Red indicates high expression, and blue indicates low expression in the heatmap.

Reference

Subramanian, A. et al . Gene set enrichment analysis: A knowledge-basedapproach for interpreting genome-wide expres- sion profiles. Proc. Natl. Acad.Sci. USA 102, 15545‒15550 (2005).

Powered Literature by Novogene

Year Journal Title

2018 Cell Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2 -Aberrant Solid Tumors

Armadillo repeat containing 12 promotes neuroblastoma progression through interaction 2018 Nat Commun with retinoblastoma binding protein 4

E6 protein expressed by high-risk HPV activates super-enhancers of the EGFR and c-MET 2018 Cancer Res oncogenes by destabilizing the histone KDM5C

Pold3 is required for genomic stability and telomere integrity in embryonic stem cells Nucleic Acids Res 2018 and meiosis

Single-Base Methylome Analysis Reveals Dynamic Epigenomic Differences Associated 2018 Plant Biotechnol J with Water Deficit in Apple

A Critical Role of Presynaptic Cadherin/Catenin/ p140Cap Complexes in Stabilizing 2017 Neuron Spines and Functional Synapses in the Neocortex

The genome of the medicinal plant Macleaya cordata provides new insights into 2017 Mol Plant benzylisoquinoline alkaloids metabolism

SIRT6 Controls Hematopoietic Stem Cell Homeostasis through Epigenetic Regulation 2016 Cell Stem Cell of Wnt Signaling

Novogene Corporation Inc.

8801 Folsom Blvd #290, Sacramento, CA 95826

916-252-0068-383 [email protected] en.novogene.com Follow us on LinkedIn