Publications - Jaime Anguiano - Page 1

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 Electronic supplementary material The online version of this article doi 10 1186 s12943-015-0485-z contains supplementary material which is available to authorized users

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