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HOX antisense lincRNA HOXA‐AS2 is an apoptosis repressor in all Trans retinoic acid treated NB4 promyelocytic leukemia cells
Author(s) -
Zhao Hang,
Zhang Xueqing,
Frazão Josias Brito,
CondinoNeto Antonio,
Newburger Peter E.
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24586
Subject(s) - retinoic acid , gene knockdown , apoptosis , acute promyelocytic leukemia , microbiology and biotechnology , biology , cancer research , tretinoin , myeloid leukemia , chemistry , cell culture , biochemistry , genetics
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.