Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells.
Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells.
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长非编码RNA MEG3与p53蛋白相互作用并调节肝癌细胞中的部分p53靶基因
DOI：
10.1371/journal.pone.0139790
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Zhu J;Liu S;Ye F;Shen Y;Tie Y;Zhu J;Wei L;Jin Y;Fu H;Wu Y;Zheng X
母系表达基因3（MEG 3）编码一种lncRNA，其被认为具有肿瘤抑制剂的功能。以前的研究表明，MEG 3通过激活p53发挥作用，然而，MEG 3的功能特性仍然不清楚，其与人类疾病的相关性正在不断研究中。在此，我们试图阐明MEG 3和p53的关系，以及在肝癌细胞中的后果。我们发现MEG 3的表达构建体的转染增强了p53的稳定性和转录活性。MEG 3的缺失分析证实，MEG 3的全长和完整结构对于其激活p53介导的反式激活是至关重要的。有趣的是，我们的研究结果首次证明MEG 3可以与p53 DNA结合结构域相互作用，并且在肝癌细胞中MEG 3过表达后，各种p53靶基因被失调。此外，qRT-PCR的结果显示，与相邻的非肿瘤样品相比，MEG 3 RNA在大多数HCC样品中丢失或减少。MEG 3在肝癌细胞中的异位表达显著抑制增殖并诱导凋亡。总之，我们的数据表明，MEG 3作为一种肿瘤抑制剂在肝癌细胞中通过与p53蛋白相互作用，激活p53介导的转录活性，并影响部分p53靶基因的表达。
Maternally Expressed Gene 3 (MEG3) encodes a lncRNA which is suggested to function as a tumor suppressor. Previous studies suggested that MEG3 functioned through activation of p53, however, the functional properties of MEG3 remain obscure and their relevance to human diseases is under continuous investigation. Here, we try to illuminate the relationship of MEG3 and p53, and the consequence in hepatoma cells. We find that transfection of expression construct of MEG3 enhances stability and transcriptional activity of p53. Deletion analysis of MEG3 confirms that full length and intact structure of MEG3 are critical for it to activate p53-mediated transactivation. Interestingly, our results demonstrate for the first time that MEG3 can interact with p53 DNA binding domain and various p53 target genes are deregulated after overexpression of MEG3 in hepatoma cells. Furthermore, results of qRT-PCR have shown that MEG3 RNA is lost or reduced in the majority of HCC samples compared with adjacent non-tumorous samples. Ectopic expression of MEG3 in hepatoma cells significantly inhibits proliferation and induces apoptosis. In conclusion, our data demonstrates that MEG3 functions as a tumor suppressor in hepatoma cells through interacting with p53 protein to activate p53-mediated transcriptional activity and influence the expression of partial p53 target genes.