Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia.
Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia.
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DOI：
10.1038/s41375-018-0110-4
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发表时间：
2018-10
期刊：
影响因子：
11.4
通讯作者：
Sanda T
中科院分区：
文献类型：
--
作者：
Ngoc PCT;Tan SH;Tan TK;Chan MM;Li Z;Yeoh AEJ;Tenen DG;Sanda T
TAL1/SCL是T细胞急性淋巴细胞白血病(T-ALL)中最常见的癌基因之一。TAL1及其调控伙伴(GATA3、RUNX1和MYB)在T-ALL细胞中相互正向调节并协同调节其下游靶基因的表达。然而，受这些因素调控的长非编码RNA(LncRNAs)在很大程度上是未知的。在这里，我们建立了一个生物信息学管道，并分析了深度覆盖的RNA-seq数据集，以确定T-ALL细胞中受TAL1调控的lncRNAs。我们的分析预测了57个假定的由TAL1激活的lncRNA。其中许多转录本受到GATA3、RUNX1和MYB的协调调控。我们发现了两个新的转录本，它们在多个T-ALL细胞样本中被激活，但在正常胸腺细胞中下调。在TAL1阳性的T-ALL病例中，ARID5B基因位点附近的一个转录本特异表达。位于FAM49A和MYCN基因之间的另一个转录本也在正常造血干细胞和T细胞前体细胞中表达。此外，我们还鉴定了T-ALL细胞中受TAL1负调控和E蛋白正调控的一组lncRNAs。这包括一个已知的位于RORC基因附近的lncRNA(lnc-OAZ3-2：7)，它在正常胸腺细胞中表达，但在TAL1阳性的T-ALL细胞中被抑制。
TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57 putative lncRNAs that are activated by TAL1. Many of these transcripts were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One transcript near the ARID5B gene locus was specifically expressed in TAL1-positive T-ALL cases. The other transcript located between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic stem cells and T-cell progenitor cells. In addition, we identified a subset of lncRNAs that were negatively regulated by TAL1 and positively regulated by E-proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3–2:7) located near the RORC gene, which was expressed in normal thymocytes but repressed in TAL1-positive T-ALL cells.
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影响因子：
11.4
作者：
Liau WS;Tan SH;Ngoc PCT;Wang CQ;Tergaonkar V;Feng H;Gong Z;Osato M;Look AT;Sanda T
通讯作者：
Sanda T
影响因子：
64.8
作者：
Kwiatkowski, Nicholas;Zhang, Tinghu;Rahl, Peter B.;Abraham, Brian J.;Reddy, Jessica;Ficarro, Scott B.;Dastur, Anahita;Amzallag, Arnaud;Ramaswamy, Sridhar;Tesar, Bethany;Jenkins, Catherine E.;Hannett, Nancy M.;McMillin, Douglas;Sanda, Takaomi;Sim, Taebo;Kim, Nam Doo;Look, Thomas;Mitsiades, Constantine S.;Weng, Andrew P.;Brown, Jennifer R.;Benes, Cyril H.;Marto, Jarrod A.;Young, Richard A.;Gray, Nathanael S.
通讯作者：
Gray, Nathanael S.
影响因子：
30.5
作者：
Miyazaki, Masaki;Rivera, Richard R.;Miyazaki, Kazuko;Lin, Yin C.;Agata, Yasutoshi;Murre, Cornelis
通讯作者：
Murre, Cornelis
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
30.5
作者：
Casero D;Sandoval S;Seet CS;Scholes J;Zhu Y;Ha VL;Luong A;Parekh C;Crooks GM
通讯作者：
Crooks GM