Open AccessWT‐CLS1 is a rhabdoid tumor cell line and can be inhibited by miR ‐16
Author(s) -
Stroup Emily Kunce,
Yeu Yunku,
Budhipramono Albert,
Hwang Tae Hyun,
Rakheja Dinesh,
ErdreichEpstein Anat,
Laetsch Theodore W.,
Amatruda James F.,
Chen Kenneth S.
Publication year - 2019
Publication title -
cancer reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.261
H-Index - 5
ISSN - 2573-8348
DOI - 10.1002/cnr2.1110
Subject(s) - wilms' tumor , microrna , cancer research , biology , cell cycle , cell growth , cell culture , tumor suppressor gene , smarcb1 , suppressor , cell , gene , gene expression , genetics , carcinogenesis , chromatin remodeling
Background Wilms tumor and rhabdoid tumor can have similar clinical presentations, but they have distinct histological and biological features. For instance, Wilms tumors commonly bear mutations in kidney differentiation or microRNA processing genes, whereas rhabdoid tumor is characterized by loss of SMARCB1 . Aims We initially set out to characterize and identify tumor suppressor microRNAs in WT‐CLS1, which had been described as a Wilms tumor cell line. Methods and Results We characterized the cell line WT‐CLS1 by whole exome sequencing, RNA‐seq, and xenograft histology. We measured the effect of microRNA overexpression on WiT49, WT‐CLS1, BT‐12, and CHLA‐06‐ATRT. We found that miR‐16 significantly impairs cell proliferation in WT‐CLS1 by repressing numerous cell cycle genes, including the D‐type cyclins. In addition, we found that the WT‐CLS1 cell line demonstrates the classic histological, mutational, and transcriptional hallmarks of rhabdoid tumor, including SMARCB1 loss. Lastly, miR‐16 also represses cell cycle genes and impairs proliferation in the BT‐12 and CHLA‐06‐ATRT rhabdoid tumor cell lines. Conclusions The loss of SMARCB1 warrants reclassification of WT‐CLS1 as rhabdoid tumor. Overexpression of miR‐16 significantly abrogates proliferation of WT‐CLS1 and other rhabdoid tumor cell lines. Further studies are necessary to gain insight into the potential for miR‐16 to be a tumor suppressor or a novel therapeutic in rhabdoid tumor.