LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression
LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression
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LncRNA ST8SIA6-AS1通过调节MAGEA3和DCAF4L2表达促进肝细胞癌进展
DOI：
10.1016/j.bbrc.2020.09.115
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Li, Lihua
中科院分区：
文献类型：
--
作者：
Zhang, Xiufen;Xu, Sui;Li, Lihua
肝细胞癌是最常见的肝癌类型。本研究旨在探讨lncRNA ST8SIA6-AS1在肝细胞癌中的作用及机制。我们发现，ST8SIA6-AS1在肝细胞癌组织中表达上调，并与TCGA患者总体生存率较低有关。此外，ST8SIA6-AS1在肝癌内部组织和细胞中高表达，ST8SIA6-AS1上调与肿瘤的侵袭性表型和患者的总体生存不良有关。ST8SIA6-AS1基因的下调在体外抑制肝癌细胞的增殖、迁移和侵袭，在体内抑制肝癌的发生。在机制上，ST8SIA6-AS1调控黑色素瘤相关抗原(MAGE)-A3(MAGEA3)和DDB1-和CUL4相关因子4-样2(DCAF4L2)的表达，救援实验证实ST8SIA6-AS1通过调节MAGEA3和DCAF4L2在肝细胞癌中发挥促肿瘤作用。ST8SIA6-AS1部分直接与miR-129-5p结合，作为竞争内源性RNA(CerNA)，促进miR-129-5p靶基因DCAF4L2的表达，发挥其在肝细胞癌中的作用。综上所述，我们的结果证实ST8SIA6-AS1是一种预测肝癌患者不良临床结局的致癌lncRNA。这些发现表明，ST8SIA6-AS1是一种潜在的肝癌治疗靶点。(C)2020 Elsevier Inc.保留所有权利。
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. In this study, we aimed to explore the role and mechanism of lncRNA ST8SIA6-AS1 in HCC. We found that ST8SIA6-AS1 was upregulated in HCC tissues and associated with poorer overall survival of HCC patients from TCGA. Moreover, ST8SIA6-AS1 was highly expressed in HCC in-house tissues and cells, and ST8SIA6-AS1 upregulation was related to aggressive tumor phenotypes and the poor overall survival of HCC patients. Downregulation of ST8SIA6-AS1 suppressed HCC cell proliferation, migration and invasion in vitro and restrained HCC tumorigenesis in vivo. In terms of mechanism, ST8SIA6-AS1 regulated melanomaassociated antigen (MAGE)-A3 (MAGEA3) and DDB1-and Cul4-associated factor 4-like 2 (DCAF4L2) expression, and rescue experiments verified that ST8SIA6-AS1 played a protumorigenic role in HCC via the regulation of MAGEA3 and DCAF4L2. ST8SIA6-AS1 partly directly bound to miR-129-5p and functioned as a competing endogenous RNA (ceRNA), subsequently facilitating the expression of the miR-129-5p target gene DCAF4L2 to play its role in HCC. In summary, our results identified ST8SIA6-AS1 as an oncogenic lncRNA predicting poor clinical outcomes of patients with HCC. These findings suggest that ST8SIA6-AS1 is a potential therapeutic target for HCC. (C) 2020 Elsevier Inc. All rights reserved.