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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

Authors: Thilini R. Fernando, Jorge R. Contreras, Matteo Zampini, Norma I. Rodriguez-Malave, Michael O. Alberti, Jaime Anguiano, Tiffany M. Tran, Jayanth K. Palanichamy, Jasmine Gajeton, Nolan M. Ung, Cody J. Aros, Ella V. Waters, David Casero, Giuseppe Basso, Martina Pigazzi, Dinesh S. Rao

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia.

Results

CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter.

Conclusions

Our findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action.
Appendix
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Metadata
Title
The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia
Authors
Thilini R. Fernando
Jorge R. Contreras
Matteo Zampini
Norma I. Rodriguez-Malave
Michael O. Alberti
Jaime Anguiano
Tiffany M. Tran
Jayanth K. Palanichamy
Jasmine Gajeton
Nolan M. Ung
Cody J. Aros
Ella V. Waters
David Casero
Giuseppe Basso
Martina Pigazzi
Dinesh S. Rao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0692-x

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