title: HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells.
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.
authors: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Hang
authors: H
authors: Zhao
authors: Xueqing
authors: X
authors: Zhang
authors: Josias Brito
authors: JB
authors: Frazão
authors: Antonio
authors: A
authors: Condino-Neto
authors: Peter E
authors: PE
authors: Newburger
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017304:Annexin A5; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D007371:Interferon-gamma
keywords: APOPTOSIS; Hox GENE CLUSTER; LONG INTERGENIC NON-CODING RNA (lincRNA); MYELOID; NON-CODING RNA
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