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Journal of Cellular Biochemistry

HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all Trans retinoic acid treated NB4 promyelocytic leukemia cells

Authors

  • Hang Zhao,

    1. Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Xueqing Zhang,

    1. Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Josias Brito Frazão,

    1. Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts
    2. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Antonio Condino-Neto,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Peter E. Newburger

    Corresponding author
    1. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts
    • Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts
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Correspondence to: Peter E. Newburger, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655. E-mail: peter.newburger@umassmed.edu

ABSTRACT

HOXA cluster antisense RNA 2 (HOXA-AS2) is a long non-coding RNA located between the HOXA3 and HOXA4 genes in the HOXA cluster. Its transcript is expressed in NB4 promyelocytic leukemia cells and human peripheral blood neutrophils, and expression is increased in NB4 cells treated with all trans retinoic acid (ATRA). Knockdown of HOXA-AS2 expression by transduced shRNA decreases the number of viable cells and increases the proportion of apoptotic cells, measured by annexin V binding and by activity and cleavage of caspases-3, -8, and -9. The increase in death of HOXA-AS2 knockdown cells was accompanied by an elevated TNF-related apoptosis-inducing ligand (TRAIL) levels, but ATRA-induced NB4 cells treated with TRAIL did show an increase in HOXA-AS2 expression. These results demonstrate that ATRA induction of HOXA-AS2 suppresses ATRA-induced apoptosis, possibly through a TRAIL-mediated pathway. HOXA-AS2-mediated negative regulation thus contributes to the fine-tuning of apoptosis during ATRA-induced myeloid differentiation in NB4 cells. J. Cell. Biochem. 114: 2375–2383, 2013. © 2013 Wiley Periodicals, Inc.

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