CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation.
CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation.
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DOI：
10.1038/srep25219
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Ciafrè SA
中科院分区：
文献类型：
--
作者：
Galardi S;Petretich M;Pinna G;D'Amico S;Loreni F;Michienzi A;Groisman I;Ciafrè SA
细胞质元件结合蛋白 1 (CPEB1) 通过 3' 非翻译区 (3'UTR) 控制 mRNA 翻译效率，调节从细胞周期控制到学习和记忆形成等许多重要的生物过程。在本研究中，我们发现 CPEB1 在人多形性胶质母细胞瘤 (GBM) 组织中显着下调，并且其表达的恢复会损害神经胶质瘤细胞系的生长。我们证明CPEB1通过特异性靶向其3'UTR来促进细胞周期抑制剂p27Kip1的表达，并在3'UTR的重叠位点与miR-221/222竞争结合，从而损害miR-221/222抑制活性。与 p27Kip1 3'UTR 结合后，CPEB1 促进聚腺苷酸尾的延长以及随后 p27Kip1 mRNA 的翻译。这导致细胞中 p27Kip1 水平升高，进而显着抑制细胞增殖，并赋予 CPEB1 作为胶质母细胞瘤肿瘤抑制因子的潜在价值。
The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3′ untranslated regions (3′UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27Kip1 by specifically targeting its 3′UTR, and competes with miR-221/222 binding at an overlapping site in the 3′UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27Kip1 3′UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27Kip1 mRNA. This leads to higher levels of p27Kip1 in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma.