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miR-16 Suppresses Growth of Rhabdoid Tumor Cells

Emily Kunce Stroup, Yunku Yeu, Albert Budhipramono, Tae Hyun Hwang, Dinesh Rakheja, Anat Erdreich-Epstein, Theodore W. Laetsch, James F. Amatruda, Kenneth S. Chen
doi: https://doi.org/10.1101/219709
Emily Kunce Stroup
Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Yunku Yeu
Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Albert Budhipramono
Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Tae Hyun Hwang
Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Dinesh Rakheja
Departments of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Pathology and Laboratory Medicine, Children’s Health Children’s Medical Center, Dallas, TX, USA
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Anat Erdreich-Epstein
Departments of Pediatrics, Saban Research Institute at Children’s Hospital Los Angeles and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027ADepartments of Pathology, Saban Research Institute at Children’s Hospital Los Angeles and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027A
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Theodore W. Laetsch
Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USADepartments of Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA
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James F. Amatruda
Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USADepartments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USADepartments of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USADepartments of Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA
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Kenneth S. Chen
Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USADepartments of Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA
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ABSTRACT

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
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 22, 2017.
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miR-16 Suppresses Growth of Rhabdoid Tumor Cells
Emily Kunce Stroup, Yunku Yeu, Albert Budhipramono, Tae Hyun Hwang, Dinesh Rakheja, Anat Erdreich-Epstein, Theodore W. Laetsch, James F. Amatruda, Kenneth S. Chen
bioRxiv 219709; doi: https://doi.org/10.1101/219709
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miR-16 Suppresses Growth of Rhabdoid Tumor Cells
Emily Kunce Stroup, Yunku Yeu, Albert Budhipramono, Tae Hyun Hwang, Dinesh Rakheja, Anat Erdreich-Epstein, Theodore W. Laetsch, James F. Amatruda, Kenneth S. Chen
bioRxiv 219709; doi: https://doi.org/10.1101/219709

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