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

Research output: Contribution to journalArticlepeer-review

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. Abbreviations atypical teratoid/rhabdoid tumormicroRNAdoxycyclineoptical density at 595 nmcyclin-dependent kinase 4

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Nov 22 2017

Keywords

  • miR-16
  • rhabdoid tumor
  • WT-CLS1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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