HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells.
HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells.
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DOI：
10.1002/jcb.24586
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发表时间：
2013-10
影响因子：
4
通讯作者：
Newburger, Peter E.
中科院分区：
文献类型：
--
作者：
Zhao, Hang;Zhang, Xueqing;Frazao, Josias Brito;Condino-Neto, Antonio;Newburger, Peter E.
HOXA簇反义RNA 2(HOXA-AS2)是一种位于HOXA簇中HOXA3和HOXA4基因之间的非编码长链RNA。它的转录本在NB4早幼粒细胞白血病细胞和人外周血中性粒细胞中表达，在全反式维甲酸(ATRA)处理的NB4细胞中表达增加。转导的shRNA抑制HOXA-AS2的表达，通过膜联蛋白V结合以及caspase-3、-8和-9的活性和裂解来衡量，减少活细胞的数量，增加凋亡细胞的比例。Hoxa-AS2基因敲除细胞死亡增加的同时伴随着肿瘤坏死因子相关的凋亡诱导配体(TRAIL)水平的升高，但经TRAIL处理的ATRA诱导的NB4细胞确实表现出Hoxa-AS2表达的增加。这些结果表明，ATRA对Hoxa-AS2的诱导抑制了ATRA诱导的细胞凋亡，可能是通过TRAIL介导的途径。因此，HOXA-AS2介导的负调控有助于微调ATRA诱导NB4细胞髓系分化过程中的细胞凋亡。
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.
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影响因子：
37.3
作者：
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通讯作者：
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11.4
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