The binding of lncRNA RP11-732M18.3 with 14-3-3 β/α accelerates p21 degradation and promotes glioma growth
The binding of lncRNA RP11-732M18.3 with 14-3-3 β/α accelerates p21 degradation and promotes glioma growth
复制标题
lncRNA RP11-732M18.3 与 14-3-3 β/α 的结合加速 p21 降解并促进神经胶质瘤生长。
DOI：
10.1016/j.ebiom.2019.06.002
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发表时间：
2019-07-01
期刊：
影响因子：
11.1
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Kang, Chun-Min;Bai, Huan-Lan;Wang, Qian
背景：长链非编码RNA（lncRNA）已被鉴定为许多发育和肿瘤发生过程的调节因子。然而，大多数lncRNA在胶质瘤中的功能仍然未知，肿瘤细胞增殖的机制仍然不清楚defined.Methods：无论是在体外和体内检测，以探讨lncRNA在胶质瘤的病理生理学的作用。lncRNA阵列用于鉴定差异表达的lncRNA。采用裸鼠皮下肿瘤形成和脑原位肿瘤模型研究lncRNA在体内的功能。通过荧光激活细胞分选、集落形成和蛋白质印迹分析来分析lncRNA的体外功能。RNA荧光原位杂交和免疫沉淀被用来探索潜在的mechanism.Findings：在这里，我们描述了新发现的非编码RNA RP 11 -732M18.3，这是高度过表达的胶质瘤细胞和相互作用14-3-3 β/α，以促进胶质瘤的生长，作为一个致癌基因。lncRNA RP 11 -732 M18.3的过表达与胶质瘤细胞的增殖和体内外肿瘤的生长有关。lncRNA RP 11 -732M18.3显著促进细胞增殖和G1/S细胞周期转换。lncRNA RP 11 -732M18.3主要定位于细胞质中。从机制上讲，lncRNA RP 11 - 732 M18.3与14-3-3 β/α的相互作用增加了p21蛋白的降解。lncRNA RP 11 -732M18.3促进了泛素缀合酶E2 E1向14-3-3 β/α的募集，并且14-3-3 β/α与泛素缀合酶E2 E1（UBE 2 E1）的结合促进了p21的降解。总之，这些数据表明，lncRNA RP 11 -732M18.3通过新描述的lncRNA-蛋白质相互作用机制调节胶质瘤生长。抑制lncRNA RP 11 -732M18.3的表达可能为胶质瘤的治疗提供新的靶点。(C)2019年爱思唯尔出版
Background: Long noncoding RNAs (lncRNAs) have been identified as regulators of a number of developmental and tumorigenic processes. However, the functions of most lncRNAs in glioma remain unknown and the mechanisms governing the proliferation of tumor cells remain poorly defined.Methods: Both in vitro and in vivo assays were performed to investigate the roles of lncRNAs in the pathophysiology of gliomas. lncRNA arrays were used to identify differentially expressed lncRNAs. Subcutaneous tumor formation and a brain orthotopic tumor model in nude mice were used to investigate the functions of lncRNAs in vivo. The in vitro functions of lncRNAs were analyzed by fluorescence-activated cell sorting, colony formation, and western blot analyses. RNA fluorescence in situ hybridization and immunoprecipitation were used to explore the underlying mechanisms.Findings: Here, we describe the newly discovered noncoding RNA RP11-732M18.3, which is highly overexpressed in glioma cells and interacts with 14-3-3 beta/alpha to promote glioma growth, acting as an oncogene. Overexpression of lncRNA RP11-732 M18.3 was associated with the proliferation of glioma cells and tumor growth in vitro and in vivo. Remarkably, lncRNA RP11-732M18.3 promoted cell proliferation and G1/S cell cycle transition. lncRNA RP11-732M18.3 is predominately localized in the cytoplasm. Mechanistically, the interaction of lncRNA RP11-732M18.3 with 14-3-3 beta/alpha increases the degradation of the p21 protein. lncRNA RP11-732M18.3 promoted the recruitment of ubiquitin-conjugating enzyme E2 E1 to 14-3-3 beta/alpha and the binding of 14-3-3 beta/alpha with ubiquitin-conjugating enzyme E2 E1 (UBE2E1) promoted the degradation of p21.Interpretation: Overall these data demonstrated that lncRNA RP11-732M18.3 regulates glioma growth through a newly described lncRNA-protein interaction mechanism. The inhibition of lncRNA RP11-732M18.3 could provide a novel therapeutic target for glioma treatment. (C) 2019 Published by Elsevier B.V.