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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

BALR-6 regulates cell growth and cell survival in B-lymphoblastic leukemia

Authors: Norma I. Rodríguez-Malavé, Thilini R. Fernando, Parth C. Patel, Jorge R. Contreras, Jayanth Kumar Palanichamy, Tiffany M. Tran, Jaime Anguiano, Michael J. Davoren, Michael O. Alberti, Kimanh T. Pioli, Salemiz Sandoval, Gay M. Crooks, Dinesh S. Rao

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

A new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), has been recently described. These lncRNAs are implicated to play pivotal roles in various molecular processes, including development and oncogenesis. Gene expression profiling of human B-ALL samples showed differential lncRNA expression in samples with particular cytogenetic abnormalities. One of the most promising lncRNAs identified, designated B-ALL associated long RNA-6 (BALR-6), had the highest expression in patient samples carrying the MLL rearrangement, and is the focus of this study.

Results

Here, we performed a series of experiments to define the function of BALR-6, including several novel splice forms that we identified. Functionally, siRNA-mediated knockdown of BALR-6 in human B-ALL cell lines caused reduced cell proliferation and increased cell death. Conversely, overexpression of BALR-6 isoforms in both human and mouse cell lines caused increased proliferation and decreased apoptosis. Overexpression of BALR-6 in murine bone marrow transplantation experiments caused a significant increase in early hematopoietic progenitor populations, suggesting that its dysregulation may cause developmental changes. Notably, the knockdown of BALR-6 resulted in global dysregulation of gene expression. The gene set was enriched for leukemia-associated genes, as well as for the transcriptome regulated by Specificity Protein 1 (SP1). We confirmed changes in the expression of SP1, as well as its known interactor and downstream target CREB1. Luciferase reporter assays demonstrated an enhancement of SP1-mediated transcription in the presence of BALR-6. These data provide a putative mechanism for regulation by BALR-6 in B-ALL.

Conclusions

Our findings support a role for the novel lncRNA BALR-6 in promoting cell survival in B-ALL. Furthermore, this lncRNA influences gene expression in B-ALL in a manner consistent with a function in transcriptional regulation. Specifically, our findings suggest that BALR-6 expression regulates the transcriptome downstream of SP1, and that this may underlie the function of BALR-6 in B-ALL.
Appendix
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Metadata
Title
BALR-6 regulates cell growth and cell survival in B-lymphoblastic leukemia
Authors
Norma I. Rodríguez-Malavé
Thilini R. Fernando
Parth C. Patel
Jorge R. Contreras
Jayanth Kumar Palanichamy
Tiffany M. Tran
Jaime Anguiano
Michael J. Davoren
Michael O. Alberti
Kimanh T. Pioli
Salemiz Sandoval
Gay M. Crooks
Dinesh S. Rao
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0485-z

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