长非编码 RNA GClnc1 通过抑制 p53 信号通路促进骨肉瘤发生。
Long non-coding RNA GClnc1 promotes tumorigenesis in osteosarcoma by inhibiting p53 signaling.
机构信息
State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, PR China.
Joint Surgery Department, No.1 Hospital of Jilin University, Changchun 130021, PR China.
出版信息
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):36-42. doi: 10.1016/j.bbrc.2018.10.135. Epub 2018 Nov 16.
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.
最近的研究表明，长非编码 RNA 在人类癌症中作为重要的调节剂发挥着重要作用。研究发现 GClnc1 在胃癌中上调，发挥致癌作用。然而，GClnc1 在骨肉瘤（OS）中的生物学功能和潜在机制尚不清楚。在这里，我们报告 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，过表达 GClnc1 促进 OS 细胞生长；而敲低 GClnc1 则有完全相反的效果。一致地，过表达 GClnc1 促进 OS 细胞在体内的致瘤性。在机制上，GClnc1 直接与 p53 结合，并阻止 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 在 OS 中作为 p53 信号的新调节剂的致癌作用。
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