The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2.
The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2.
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DOI：
10.1038/s41419-023-05683-6
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发表时间：
2023-02-27
影响因子：
9
通讯作者：
Vogt, Peter K.
中科院分区：
文献类型：
--
作者：
Garcia-Caballero, Daniel;Hart, Jonathan R.;Vogt, Peter K.
MYC控制了大部分非编码基因组。最初在人B细胞系P496-3中鉴定了几个长的非编码转录物，然后显示其为MYC驱动的Burkitt淋巴瘤衍生的拉莫斯细胞增殖所需。在这项研究中，我们专门使用拉莫斯细胞作为人类B细胞谱系的代表。拉莫斯细胞增殖所需的MYC控制的lncRNA之一是ENSG 00000254887，我们将其称为LNROP（POU 2F 2的长非编码调节子）。在基因组中，LNROP位于编码OCT 2的基因POU 2F 2附近。OCT 2是一种在维持人B细胞增殖中具有重要作用的转录因子。在这里，我们表明LNROP是一种核RNA，是MYC的直接靶点。LNROP的下调减弱了OCT 2的表达。LNROP对OCT 2表达的这种影响是单向的，因为OCT 2的下调不改变LNROP的表达。我们的数据表明，LNROP是OCT 2的顺式作用调节剂。为了说明LNROP的下游范围，我们选择了OCT 2的突出靶标，酪氨酸磷酸酶SHP-1。OCT 2的下调提高了SHP-1的表达。我们的数据表明，以下相互作用的路径：LNROP使B细胞的增殖，积极和单向调节生长刺激转录因子OCT 2。在活跃增殖的B细胞中，OCT 2减弱SHP-1的表达和抗增殖活性。
MYC controls most of the non-coding genome. Several long noncoding transcripts were originally identified in the human B cell line P496-3 and then shown to be required for MYC-driven proliferation of Burkitt lymphoma-derived RAMOS cells. In this study, we used RAMOS cells exclusively as a representative of the human B cell lineage. One of the MYC-controlled lncRNAs required for RAMOS cell proliferation is ENSG00000254887 which we will term LNROP (long non-coding regulator of POU2F2). In the genome, LNROP is located in close proximity of POU2F2, the gene encoding OCT2. OCT2 is a transcription factor with important roles in sustaining the proliferation of human B cells. Here we show that LNROP is a nuclear RNA and a direct target of MYC. Downregulation of LNROP attenuates the expression of OCT2. This effect of LNROP on the expression of OCT2 is unidirectional as downregulation of OCT2 does not alter the expression of LNROP. Our data suggest that LNROP is a cis-acting regulator of OCT2. To illustrate the downstream reach of LNROP, we chose a prominent target of OCT2, the tyrosine phosphatase SHP-1. Downregulation of OCT2 elevates the expression of SHP-1. Our data suggest the following path of interactions: LNROP enables the proliferation of B cells by positively and unidirectionally regulating the growth-stimulatory transcription factor OCT2. In actively proliferating B cells, OCT2 attenuates the expression and anti-proliferative activity of SHP-1.
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影响因子：
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