PTB-AS, a Novel Natural Antisense Transcript, Promotes Glioma Progression by Improving PTBP1 mRNA Stability with SND1
PTB-AS, a Novel Natural Antisense Transcript, Promotes Glioma Progression by Improving PTBP1 mRNA Stability with SND1
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PTB-AS 是一种新型天然反义转录本，通过使用 SND1 提高 PTBP1 mRNA 稳定性来促进胶质瘤进展。
DOI：
10.1016/j.ymthe.2019.05.023
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发表时间：
2019-09-04
影响因子：
12.4
通讯作者：
Peng, Xiaozhong
中科院分区：
文献类型：
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作者：
Zhu, Liyuan;Wei, Qunfang;Peng, Xiaozhong
胶质瘤是脑内最常见的原发性恶性肿瘤，具有高复发率和致死率，因此，迫切需要阐明这种不治之症的分子机制。多聚嘧啶束结合蛋白（PTBP 1，也称为hnRNP I）是一种RNA结合蛋白，具有多种促进胶质瘤发生的机制。然而，调节PTBP 1表达的机制尚不清楚。在此，我们报告了一种新的天然反义非编码RNA，PTB-AS，其表达与PTBP 1 mRNA呈正相关。我们发现PTB-AS在体内和体外都能显著促进胶质瘤细胞的增殖和迁移。PTB-AS通过直接结合其3' UTR并稳定mRNA而显著增加PTBP 1水平。此外，葡萄球菌核酸酶结构域1（SND 1）显着增加PTB-AS和PTBP 1 mRNA之间的结合能力。从机制上讲，PTB-AS可以掩盖PTBP 1 -3' UTR中miR-9的结合位点; miR-9负调控PTBP 1。综上所述，我们发现PTB-AS，其通过在SND 1的协助下与PTBP 1 3' UTR的扩展碱基配对来维持PTBP 1水平，可以显著促进胶质瘤的发生。
Glioma, the most common primary malignancy in the brain, has high recurrence and lethality rates, and thus, elucidation of the molecular mechanisms of this incurable disease is urgently needed. Poly-pyrimidine tract binding protein (PTBP1, also known as hnRNP I), an RNA-binding protein, has various mechanisms to promote gliomagenesis. However, the mechanisms regulating PTBP1 expression are unclear. Herein, we report a novel natural antisense noncoding RNA, PTB-AS, whose expression correlated positively with PTBP1 mRNA. We found that PTB-AS significantly promoted the proliferation and migration in vivo and in vitro of glioma cells. PTB-AS substantially increased the PTBP1 level by directly binding to its 3' UTR and stabilizing the mRNA. Furthermore, staphylococcal nuclease domain-containing 1 (SND1) dramatically increased the binding capacity between PTB-AS and PTBP1 mRNA. Mechanistically, PTB-AS could mask the binding site of miR-9 in the PTBP1-3' UTR; miR-9 negatively regulates PTBP1. To summarize, we revealed that PTB-AS, which maintains the PTBP1 level through extended base pairing to the PTBP1 3' UTR with the assistance of SND1, could significantly promote gliomagenesis.