lncRNA HULC promotes the growth of hepatocellular carcinoma cells via stabilizing COX-2 protein
lncRNA HULC promotes the growth of hepatocellular carcinoma cells via stabilizing COX-2 protein
复制标题
lncRNA HULC通过稳定COX-2蛋白促进肝细胞癌细胞生长
DOI：
10.1016/j.bbrc.2017.06.103
复制
发表时间：
2017-08-26
影响因子：
3.1
通讯作者：
He, Fengtian
中科院分区：
文献类型：
--
作者：
Xiong, Haojun;Li, Bo;He, Fengtian
在肝癌中高度上调的一种在肝细胞癌中过表达的lncRNA已被证明参与了肝细胞癌的发生发展。然而，HULC促进肝癌细胞异常生长的机制尚不清楚。在本研究中，我们首次证明HULC通过上调COX-2蛋白促进肝癌细胞的生长。此外，对HULC上调COX-2的相应机制的研究表明，HULC上调泛素特异肽酶22(USP22)的水平，通过去除COX-2上的共轭多聚泛素链来降低泛素介导的COX-2蛋白的降解，最终稳定COX2蛋白。此外，USP22或COX-2基因敲除可减弱HULC介导的肝癌细胞异常生长。综上所述，我们的结果表明“USP22/COX-2”轴在HULC促进肝癌细胞生长中起重要作用。这一新途径的发现可能为开发新的潜在的抗肝癌策略铺平道路。(C)2017 Elsevier Inc.保留所有权利。
Highly upregulated in liver cancer (HULC), a lncRNA overexpressed in hepatocellular carcinoma (HCC), has been demonstrated to be involved in the carcinogenesis and progression of HCC. However, the mechanisms of HULC promoting the abnormal growth of HCC cells are still not well elucidated. In the present study, we for the first time demonstrated that HULC promoted the growth of HCC cells through elevating COX-2 protein. Moreover, the study of the corresponding mechanism by which HULC upregulated COX-2 showed that HULC enhanced the level of ubiquitin-specific peptidase 22 (USP22), which decreased ubiquitin-mediated degradation of COX-2 protein by removing the conjugated polyubiquitin chains from COX-2 and finally stabilized COX2 protein. In addition, knockdown of USP22 or COX-2 attenuated HULC-mediated abnormal growth of HCC cells. In conclusion, our results demonstrated that "USP22/COX-2" axis played an important role in HULC promoting growth of HCC cells. The identification of this novel pathway may pave a road for developing new potential anti-HCC strategies. (C) 2017 Elsevier Inc. All rights reserved.