Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells.
Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells.
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抑制长非编码RNA NEAT1会损害急性早幼粒细胞白血病细胞的骨髓分化
DOI：
10.1186/1471-2407-14-693
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发表时间：
2014-09-23
期刊：
影响因子：
3.8
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Zeng C;Xu Y;Xu L;Yu X;Cheng J;Yang L;Chen S;Li Y
急性早幼粒细胞白血病（APL）的特点是相互易位t(15;17)， PML与视黄酸受体α (RARα)融合。尽管PML-RARα对肿瘤的发病机制和治疗反应至关重要，但PML-RARα发挥其致癌潜能的分子和细胞机制尚未完全阐明。最近的报道表明，长链非编码rna （lncRNAs）有助于精确控制基因表达，并参与人类疾病。lncRNA在APL中的作用尚不清楚。我们利用实时定量逆转录pcr （qRT-PCR）分析了NEAT1在APL样品和细胞系中的表达。Western blot检测PML-RARα的表达。流式细胞术检测表面CD11b抗原表达，评估细胞分化情况。我们发现，与健康供者相比，新发APL样本中的核富集丰富转录本1 （NEAT1）显著受到抑制。NEAT1是核体副斑形成所必需的lncRNA。我们进一步提供证据表明PML-RARα抑制NEAT1的表达。此外，在全反式维甲酸（ATRA）诱导的NB4细胞分化过程中，NEAT1显著上调。最后，我们证明了NEAT1在髓细胞分化中的重要性。我们发现，通过小干扰RNA （siRNA）减少NEAT1可以阻断atra诱导的分化。我们的研究结果表明，核长链非编码RNA NEAT1的表达减少可能在APL细胞的髓系分化中起作用。本文的在线版本（doi:10.1186/1471-2407-14-693）包含补充材料，可供授权用户使用。
Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17), which fuses PML with retinoic acid receptor alpha (RARα). Although PML-RARα is crucially important for pathogenesis and responsiveness to treatment, the molecular and cellular mechanisms by which PML-RARα exerts its oncogenic potential have not been fully elucidated. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to the precise control of gene expression and are involved in human diseases. Little is known about the role of lncRNA in APL. We analyzed NEAT1 expression in APL samples and cell lines by real-time quantitative reverse transcription-PCR (qRT-PCR). The expression of PML-RARα was measured by Western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis. We found that nuclear enriched abundant transcript 1 (NEAT1), a lncRNA essential for the formation of nuclear body paraspeckles, is significantly repressed in de novo APL samples compared with those of healthy donors. We further provide evidence that NEAT1 expression was repressed by PML-RARα. Furthermore, significant NEAT1 upregulation was observed during all-trans retinoic acid (ATRA)-induced NB4 cell differentiation. Finally, we demonstrate the importance of NEAT1 in myeloid differentiation. We show that reduction of NEAT1 by small interfering RNA (siRNA) blocks ATRA-induced differentiation. Our results indicate that reduced expression of the nuclear long noncoding RNA NEAT1 may play a role in the myeloid differentiation of APL cells. The online version of this article (doi:10.1186/1471-2407-14-693) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbrc.2010.02.077
发表时间：
2010-03-19
影响因子：
3.1
作者：
Miyake, Masato;Hayashi, Shinichiro;Yamaguchi, Takahiro
通讯作者：
Yamaguchi, Takahiro
影响因子：
64.5
作者：
Spector, David L
通讯作者：
Spector, David L
影响因子：
3.6
作者：
Zeng, Cheng-Wu;Zhang, Xing-Ju;Chen, Yue-Qin
通讯作者：
Chen, Yue-Qin
影响因子：
7
作者：
Sunwoo, Hongjae;Dinger, Marcel E.;Spector, David L.
通讯作者：
Spector, David L.
影响因子：
11.4
作者：
Duprez, E;Wagner, K;Tenen, DG
通讯作者：
Tenen, DG