Long non-coding RNA GClnc1 promotes tumorigenesis in osteosarcoma by inhibiting p53 signaling
Long non-coding RNA GClnc1 promotes tumorigenesis in osteosarcoma by inhibiting p53 signaling
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DOI：
10.1016/j.bbrc.2018.10.135
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发表时间：
2018-12-09
影响因子：
3.1
通讯作者：
Li, Guangyu
中科院分区：
文献类型：
--
作者：
Sui, Yutong;Han, Yu;Li, Guangyu
最近的研究表明，长链非编码RNA作为人类癌症的重要调节因子具有重要作用。GClnc1在胃癌中表达上调，发挥致癌作用。然而，GClnc1在骨肉瘤（osteosarcoma，OS）中的生物学功能及其作用机制尚不清楚。在这里，我们报告说，GClnc1在OS组织中上调，其高表达预示着患者预后不良。功能分析表明，GClnc1的过表达促进OS细胞的生长，而GClnc1的敲低具有完全相反的效果。因此，GClnc1的过表达促进OS细胞的体内致瘤性。在机制上，GClnc1直接结合p53并阻断p53与乙酰转移酶p300的结合，从而抑制p53的乙酰化，导致p21和BAX的表达减少。这项研究揭示了lncRNA GClnc1（一种新的p53信号转导调节剂）在OS中的致癌基因作用。（C）2018由Elsevier Inc.出版。
Recent studies suggest important roles for long noncoding RNAs as essential regulators of human cancer. GClnc1 was found to be upregulated in gastric cancer, playing oncogenic roles. However, the biological function and underlying mechanism of GClnc1 in osteosarcoma (OS) remain unclear. Here, we report that GClnc1 is upregulated in OS tissues and its high expression predicts poor prognosis of patients. Functional analyses show that overexpression of GClnc1 promotes OS cells growth; whereas knockdown of GClnc1 has completely opposite effects. Consistently, overexpression of GClnc1 promotes tumorigenicity of OS cells in vivo. Mechanistically, GClnc1 directly binds to p53 and blocks the binding of p53 to acetyltransferase p300, and thereby suppresses acetylation of p53, leading to the reduced expression of p21 and BAX. This study shed light on the oncogene role of lncRNA GClnc1, a new modulator of p53 signaling, in OS. (C) 2018 Published by Elsevier Inc.