PT  - JOURNAL ARTICLE
AU  - Emily Kunce Stroup
AU  - Yunku Yeu
AU  - Albert Budhipramono
AU  - Tae Hyun Hwang
AU  - Dinesh Rakheja
AU  - Anat Erdreich-Epstein
AU  - Theodore W. Laetsch
AU  - James F. Amatruda
AU  - Kenneth S. Chen
TI  - miR-16 Suppresses Growth of Rhabdoid Tumor Cells
AID  - 10.1101/219709
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 219709
4099  - http://biorxiv.org/content/early/2017/11/22/219709.short
4100  - http://biorxiv.org/content/early/2017/11/22/219709.full
AB  - Background Rhabdoid tumor is a highly aggressive pediatric cancer characterized by biallelic loss and/or mutation of SMARCB1. Outcomes remain poor, and there are no established ways to target the tumorigenic pathways driven by SMARCB1 inactivation. SMARCB1 loss leads to an increase in cyclin D transcription.Procedure We characterized the cell line WT-CLS1, which has been described previously as Wilms tumor, by whole-exome sequencing, RNA-seq, and xenograft histology. We measured the effect of microRNA overexpression on WT-CLS1, BT-12, and CHLA-06-ATRT.Results We found that WT-CLS1 demonstrates the histological, mutational, and transcriptional hallmarks of rhabdoid tumor. Because the microRNAs let-7 and miR-16 can target cyclin D genes, we next overexpressed each of these microRNAs in WT-CLS1. We found that miR-16 reduced cell accumulation. This was accompanied by a decrease in proliferation markers and an increase in apoptosis markers. These results were replicated in the BT-12 and CHLA-06-ATRT cell lines.Conclusions The loss-of-function SMARCB1 mutation found in WT-CLS1, in conjunction with immunohistochemical and gene expression analysis, warrants reclassification of this cell line as rhabdoid tumor. Proliferation of WT-CLS1 and other rhabdoid tumor cell lines is significantly abrogated by miR-16 overexpression. Further studies are necessary to gain insight into the potential for miR-16 to be used as a novel therapeutic in rhabdoid tumor.(ATRT)atypical teratoid/rhabdoid tumor(miRNA)microRNA(dox)doxycycline(OD595)optical density at 595 nm(CDK4)cyclin-dependent kinase 4