LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway.
LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway.
复制标题
DOI：
10.18632/oncotarget.7487
复制
发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Liu L;Yue H;Liu Q;Yuan J;Li J;Wei G;Chen X;Lu Y;Guo M;Luo J;Chen R
越来越多的证据表明，长链非编码RNA（lncRNA）在转录调控中起着重要作用，而lncRNA在转录后水平上的功能还不太清楚。在本研究中，我们报告了一个名为MT1JP的lncRNA，它通过转录后机制发挥肿瘤抑制作用。我们发现，MT1JP是差异表达的肿瘤组织，通过分析数据从定制的微阵列应用到76对匹配的正常和癌症组织样本。MT1JP通过与RNA结合蛋白TIAR结合，增强了主转录因子p53的翻译，从而调控了一系列涉及p53的信号通路，如细胞周期、凋亡和增殖。当MT1JP下调时，p53蛋白水平下降，这反过来又加速了细胞退化和肿瘤形成。此外，MT1JP在癌组织和正常组织中的差异表达表明它可能是一个有前途的预后标志物和治疗靶点。总之，我们确定MT1JP作为一个关键因素，通过调节p53的翻译，通过与TIAR的相互作用，抑制细胞转化，这一发现很可能为未来的研究揭示了新的光在细胞转化过程中的lncRNA的转录后或翻译的影响。
Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play important roles in transcriptional regulation, whereas the extent to which the lncRNAs also function at the posttranscriptional level is less known. In the present study, we report a lncRNA named MT1JP which acts as a tumor suppressor through a posttranscriptional mechanism. We found that MT1JP is differentially expressed in tumor tissues by analyzing data from a customized microarray applied to 76 pairs of matched normal and cancer tissue samples. By associating with the RNA-binding protein TIAR, MT1JP enhanced the translation of the master transcription factor p53, thereby regulating a series of pathways involving p53, such as the cell cycle, apoptosis and proliferation. When MT1JP was down-regulated, the protein level of p53 declined, which in turn accelerated cell deterioration and tumor formation. Moreover, differential expression of MT1JP in cancerous and normal tissues suggests that it may be a promising prognostic marker and a therapeutic target. Taken together, we identified MT1JP as a critical factor in restraining cell transformation by modulating p53 translation through interactions with TIAR, and this finding is likely to shed new light on future investigations about posttranscriptional or translational effects of lncRNAs during cell transformation.