Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia.
Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia.
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DOI：
10.18632/oncotarget.12063
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发表时间：
2016-11-08
期刊：
影响因子：
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通讯作者：
Van Vlierberghe P
中科院分区：
文献类型：
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作者：
Ghazavi F;De Moerloose B;Van Loocke W;Wallaert A;Helsmoortel HH;Ferster A;Bakkus M;Plat G;Delabesse E;Uyttebroeck A;Van Nieuwerburgh F;Deforce D;Van Roy N;Speleman F;Benoit Y;Lammens T;Van Vlierberghe P
大量证据表明，长链非编码RNA在肿瘤发生中起重要作用。然而，它们在儿童B细胞前体急性淋巴细胞白血病的分子发病机制中的作用尚未得到广泛探讨。在这里，我们对ETV 6/RUNX 1阳性BCP-ALL（儿科白血病最常见的亚型之一）中的长非编码RNA转录组进行了全面分析。首先，我们使用原发性白血病患者样本来鉴定由596个lncRNA转录物组成的ETV 6/RUNX 1特异性表达特征。接下来，将该lncRNA特征与BCP-ALL细胞系的RNA测序和ETV 6/RUNX 1敲低的体外模型系统的lncRNA谱整合，揭示了lnc-NKX 2 -3-1、lnc-TIMM 21 -5、lnc-ASTN 1 -1和lnc-RTN 4 R-1确实受致癌融合蛋白调节。此外，在ETV 6/RUNX 1阳性细胞中，lnc-RTN 4 R-1和lnc-NKX 2 -3-1的持续失活引起基因表达的显著变化。总之，我们的研究确定了与ETV 6/RUNX 1阳性BCP-ALL相关的独特lncRNA表达特征，并将lnc-RTN 4 R-1和lnc-NKX 2 -3-1鉴定为lncRNA，其可能在功能上与这种流行的人类白血病亚型的生物学有关。
Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their role in the molecular pathogenesis of pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1-positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. First, we used primary leukemia patient samples to identify an ETV6/RUNX1 specific expression signature consisting of 596 lncRNA transcripts. Next, integration of this lncRNA signature with RNA sequencing of BCP-ALL cell lines and lncRNA profiling of an in vitro model system of ETV6/RUNX1 knockdown, revealed that lnc-NKX2-3-1, lnc-TIMM21-5, lnc-ASTN1-1 and lnc-RTN4R-1 are truly regulated by the oncogenic fusion protein. Moreover, sustained inactivation of lnc-RTN4R-1 and lnc-NKX2-3-1 in ETV6/RUNX1 positive cells caused profound changes in gene expression. All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.