Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells
Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells
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DOI：
10.1016/j.bbrc.2018.03.215
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发表时间：
2018-05-15
影响因子：
3.1
通讯作者：
Wang, Lu-Wen
中科院分区：
文献类型：
--
作者：
Chen, Hui;Yang, Fan;Wang, Lu-Wen
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。最近的研究报道，IncRNA LINC00473 （LNC473）参与了癌症的进展。然而，LNC473在HCC进展中的临床意义和功能作用尚不清楚。在本研究中，我们发现LNC473在HCC组织中的表达明显升高，且与肿瘤大小较大、BCLC分期较高、血管受侵及预后不良相关。功能增益和功能损失分析显示，LNC473增强HCC细胞的增殖和侵袭，并诱导上皮间充质转化（EMT）过程。机制上，LNC473与癌蛋白survivin相关并调控其稳定性。LNC473可以募集去泛素酶USP9X抑制survivin的泛素化水平，进而增加survivin的表达。因此，我们的研究结果提示，LNC473作为癌基因在HCC进展中发挥其功能，可能成为HCC治疗的治疗靶点。(C) 2018年Elsevier Inc.出版
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Recent studies reported that IncRNA LINC00473 (LNC473) was involved in cancer progression. However, the clinical significance and functional role of LNC473 in HCC progression is still unknown. In the present study, we found that the LNC473 expression was markedly elevated in HCC tissues and correlated with bigger tumor size, higher BCLC stage, vascular invasion and poor prognosis. Gain- and loss-of-function assay showed that LNC473 enhanced HCC cell proliferation and invasion and induced epithelial mesenchymal transition (EMT) process. Mechanistically, LNC473 associated with oncoprotein survivin and regulates its stability. Moreover, LNC473 could recruit deubiquitinase USP9X to inhibit the ubiquitination level of survivin and then increase survivin expression. Therefore, our results suggest that LNC473 exerts its functions as an oncogene in HCC progression and may be a therapeutic target for HCC treatment. (C) 2018 Published by Elsevier Inc.