RESEARCH Open Access The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia Thilini R. Fernando 1,9 , Jorge R. Contreras 1,2 , Matteo Zampini 3 , Norma I. Rodriguez-Malave 1,2,9 , Michael O. Alberti 1,10 , Jaime Anguiano 1,11 , Tiffany M. Tran 1,4 , Jayanth K. Palanichamy 1,12 , Jasmine Gajeton 5,13 , Nolan M. Ung 1 , Cody J. Aros 6 , Ella V. Waters 1,14 , David Casero 1 , Giuseppe Basso 3 , Martina Pigazzi 3 and Dinesh S. Rao 1,7,8* 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. Keywords: Non-coding RNA, CASC15, ETV6-RUNX1, SOX4, B-all Background Among the several classes of non-coding RNA species be- ing described, long non-coding RNAs are notable for their status as unique gene structures [1]. The majority of lncRNAs is characterized by capped, polyadenylated, and spliced transcripts that lack an open reading frame. Genes encoding lncRNAs show positional conservation in the genome and contain very short stretches of highly con- served sequences between species [1–3]. Despite the simi- larities in their genetic organization, there is a great deal of variation in the functions of different lncRNAs. They play a variety of roles at the cellular level, including regu- lation of transcription and translation, leading to alterations in gene expression. One of these functions is the regulation of gene expression in cis, which results in the modulation of expression of chromosomally adjacent genes upon knockdown or overexpression of lncRNAs [4]. Our recent work has identified a list of lncRNAs that are differentially expressed in pediatric B-lymphoblastic leukemia (B-ALL) patient samples [5]. One of the lncRNAs from our study, annotated as CASC15, (previ- ously annotated as LINC00340) was of particular interest as it neighbors the protein coding gene, SOX4. SOX4 was first identified as a transcriptional activator in lymphocytes and plays an essential role in B-cell development [6, 7]. Recent studies have shown involvement of SOX4 in many human malignancies, including the hematopoietic system [8, 9]. CASC15 was recently described in two other types of cancer: neuroblastoma and melanoma. It is lost as part of the chromosome 6p22 deletion in neuroblastoma, and * Correspondence: drao@mednet.ucla.edu 1 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, USA 7 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, USA Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fernando et al. Molecular Cancer (2017) 16:126 DOI 10.1186/s12943-017-0692-x