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长链非编码RNA MT1JP通过与TIAR相互作用来调节p53信号通路,从而发挥肿瘤抑制作用。

LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway.

作者信息

Liu Lihui, Yue Haiyan, Liu Qinghua, Yuan Jiao, Li Jing, Wei Guifeng, Chen Xiaomin, Lu Youyong, Guo Mingzhou, Luo Jianjun, Chen Runsheng

机构信息

Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Oncotarget. 2016 Mar 29;7(13):15787-800. doi: 10.18632/oncotarget.7487.

Abstract

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.

摘要

越来越多的证据表明,长链非编码RNA(lncRNA)在转录调控中发挥重要作用,然而lncRNA在转录后水平发挥作用的程度却鲜为人知。在本研究中,我们报道了一种名为MT1JP的lncRNA,它通过转录后机制发挥肿瘤抑制作用。通过分析应用于76对匹配的正常和癌组织样本的定制微阵列数据,我们发现MT1JP在肿瘤组织中差异表达。通过与RNA结合蛋白TIAR结合,MT1JP增强了主要转录因子p53的翻译,从而调控了一系列涉及p53的通路,如细胞周期、凋亡和增殖。当MT1JP下调时,p53的蛋白水平下降,进而加速细胞恶化和肿瘤形成。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景的预后标志物和治疗靶点。综上所述,我们确定MT1JP是通过与TIAR相互作用调节p53翻译来抑制细胞转化的关键因子,这一发现可能为未来关于lncRNA在细胞转化过程中的转录后或翻译作用的研究提供新的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6dd/4941277/87bfc71fe43a/oncotarget-07-15787-g001.jpg

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