Junge Alexander, Zandi Roza, Havgaard Jakob Hull, Gorodkin Jan, Cowland Jack Bernard
Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
Gene. 2017 Jun 5;615:35-40. doi: 10.1016/j.gene.2017.03.015. Epub 2017 Mar 16.
t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts in t(8;21) AML, compared to normal hematopoietic cells. We investigated the role of highly-upregulated RUNX1T1 under the hypothesis that it acts as competing endogenous RNA (ceRNA) titrating microRNAs (miRNAs) away from their target transcripts and thus contributes to AML formation. Using publicly available t(8;21) AML RNA-Seq and miRNA-Seq data available from The Cancer Genome Atlas (TCGA) project, we obtained a network consisting of 605 genes that may act as ceRNAs competing for miRNAs with the suggested RUNX1T1 miRNA sponge. Among the 605 ceRNA candidates, 121 have previously been implied in cancer development. Players in the integrin, cadherin, and Wnt signaling pathways affected by the RUNX1T1 sponge were overrepresented. Finally, among a set of 21 high interest RUNX1T1 ceRNAs we found multiple genes that have previously been linked to AML formation. In conclusion, our study offers a novel look at the role of the RUNX1-RUNX1T1 fusion transcript in t(8;21) AML beyond previously investigated genetic and epigenetic aberrations.
t(8;21)急性髓系白血病（AML）的特征是8号和21号染色体之间发生易位，并形成独特的RUNX1-RUNX1T1融合转录本。这种易位使RUNX1T1受RUNX1启动子的控制，导致与正常造血细胞相比，t(8;21) AML中RUNX1T1转录本显著上调。我们研究了高度上调的RUNX1T1的作用，其假设是它作为竞争性内源RNA（ceRNA），将微小RNA（miRNA）从其靶转录本上滴定下来，从而促进AML的形成。利用从癌症基因组图谱（TCGA）项目获得的公开可用的t(8;21) AML RNA测序和miRNA测序数据，我们获得了一个由605个基因组成的网络，这些基因可能作为ceRNA与建议的RUNX1T1 miRNA海绵竞争miRNA。在605个ceRNA候选基因中，有121个先前已被认为与癌症发展有关。受RUNX1T1海绵影响的整合素、钙黏着蛋白和Wnt信号通路中的参与者比例过高。最后，在一组21个高度关注的RUNX1T1 ceRNA中，我们发现了多个先前与AML形成相关的基因。总之，我们的研究为RUNX1-RUNX1T1融合转录本在t(8;21) AML中的作用提供了新的视角，超越了先前研究的遗传和表观遗传异常。
