LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1
LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1
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DOI：
10.3389/fcell.2020.00142
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发表时间：
2020-03-26
影响因子：
5.5
通讯作者：
Chen, Feihu
中科院分区：
文献类型：
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作者：
Feng, Yubin;Hu, Shuang;Chen, Feihu
大量证据表明，长链非编码RNA（longnoncodingRNA，lncRNA）在肿瘤的发生、发展中起着重要的调控作用。大多数lncRNA已被证明在急性髓细胞白血病（AML）中具有生物学和临床意义，但仍需进一步研究。在本研究中，我们研究了lncRNA NR-104098在AML中的作用及其具体机制。对NB 4细胞进行微阵列分析。基于相关分析结果，我们确定lncRNA NR-104098是在AML细胞中显著上调的抑制基因。LncRNA NR-104098在体外可抑制AML细胞增殖并诱导其分化，在小鼠移植瘤中也发挥主要作用。在机械上，证实了lncRNA NR-104098可以通过直接结合E2 F1并将E2 F1募集到EZH 2启动子来有效抑制EZH 2转录。此外，ATPR可显著增加NR-104098的表达，而敲低NR-104098可抑制ATPR对AML细胞增殖和诱导分化的抑制作用。总之，这些结果导致对ATPR诱导的AML分化的机制的更深入的了解，并通过在转录水平上抑制EZH 2来防止增殖。
Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Most lncRNAs have been proven to have biological and clinical significance in acute myeloid leukemia (AML), but further investigation remains necessary. In this study, we investigated lncRNA NR-104098 in AML and its specific mechanism. The microarray analysis was performed on NB4 cells. Based on the related analysis results, we identified that lncRNA NR-104098 is a suppressor gene that is significantly upregulated in AML cells. LncRNA NR-104098 could inhibit proliferation and induce differentiation in AML cells in vitro and also play main role in the mouse xenografts. Mechanically, it was confirmed that lncRNA NR-104098 may effectively inhibit EZH2 transcription by directly binding to E2F1 and recruiting E2F1 to the EZH2 promoter. In addition, ATPR can significantly increase the expression of lncRNA NR-104098, whereas knocking down NR104098 can inhibit the inhibitory effect of ATPR on the proliferation and induction differentiation of AML cells. Taken together, these results lead to deeper insight into the mechanism of ATPR-induced AML differentiation and prevent proliferation by inhibiting EZH2 on the transcriptional level.