The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.
The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.
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DOI：
10.1186/s13059-017-1331-y
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发表时间：
2017-10-27
期刊：
影响因子：
12.3
通讯作者：
Huarte M
中科院分区：
文献类型：
--
作者：
Marín-Béjar O;Mas AM;González J;Martinez D;Athie A;Morales X;Galduroz M;Raimondi I;Grossi E;Guo S;Rouzaut A;Ulitsky I;Huarte M
现在很明显，大多数细胞转录本不编码蛋白质，其中一个重要的子集是长链非编码rna （lncrna）。许多lncrna在癌症中表现出异常表达，其中一些与细胞转化有关。然而，潜在的机制仍然知之甚少，lncRNA的序列如何决定它们的功能尚不清楚。在这里，我们描述了p53调控的人类lncRNA LINC-PINT在癌症中的功能。我们发现LINC-PINT在多种类型的癌症中下调，并通过降低癌细胞的侵袭性表型而作为肿瘤抑制lncRNA。跨物种分析确定了LINC-PINT中高度保守的序列元素，这对其功能至关重要。该序列介导了与PRC2的特异性相互作用，这对于由转录因子EGR1调节的基因的linc - pint依赖性的前入侵特征的抑制是必要的。我们的研究结果支持了LINC-PINT和PRC2之间保守的功能共依赖，并使我们提出了一种新的机制，其中lncRNA调节在共调节基因组位点附近的自由PRC2的可用性。本文的在线版本（doi:10.1186/s13059-017-1331-y）包含补充材料，仅供授权用户使用。
It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci. The online version of this article (doi:10.1186/s13059-017-1331-y) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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