Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma
Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma
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SNHG6 的上调通过竞争性结合 miR-101-3p 并与肝细胞癌中的 UPF1 相互作用来调节 ZEB1 表达
DOI：
10.1016/j.canlet.2016.09.034
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发表时间：
2016-12-28
期刊：
影响因子：
9.7
通讯作者：
Liu, Quanyan
中科院分区：
文献类型：
--
作者：
Chang, Lei;Yuan, Yufeng;Liu, Quanyan
新出现的证据表明，小核仁RNA（snoRNA）和它们的宿主基因（SNHGs）在人类癌症的发展中具有功能障碍的作用。我们使用人体组织和细胞系在全球范围内研究了snoRNA宿主基因6（SNHG 6）促进肝细胞癌（HCC）进展的分子机制。我们发现SNHG 6在HCC组织和肝癌细胞系中过表达，并且与HCC患者的组织学分级、B型肝炎病毒DNA、巴塞罗那临床肝癌分期和门静脉癌栓密切相关。敲低SNHG 6诱导肝癌细胞系凋亡和抑制细胞周期进程，而转基因表达SNHG 6在永生化人肝细胞系L02中具有相反的效果。从SNHG 6敲低细胞生长的异种移植肿瘤的平均体积小于从对照细胞生长的肿瘤。SNHG 6可能作为竞争性内源RNA，有效地成为miR-101- 3 p的汇，从而调节锌指E-box结合同源框1的去阻遏，施加额外水平的转录后调节。在功能上，SNHG 6通过诱导上皮细胞向间质细胞转化促进肿瘤生长和转移。进一步的研究表明SNHG 6可能通过与上移码蛋白1结合并调节Smad 7的表达而影响肝癌的发生。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have malfunctioning roles in the development of human cancers. We globally investigated the molecular mechanisms by which snoRNA host gene 6 (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in hepatoma cell lines and is closely associated with histologic grade, hepatitis B virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in patients with HCC. Knockdown of SNHG6 induced apoptosis and repressed cell cycle progression in hepatoma cell lines, whereas transgenic expression of SNHG6 in the immortalized human hepatic cell line L02 had opposite effects. Xenograft tumors grown from SNHG6-knockdown cells had smaller mean volumes than did tumors grown from control cells. SNHG6 may act as a competing endogenous RNA, effectively becoming a sink for miR-101-3p and thereby modulating the derepression of zinc finger E-box binding homeobox 1, imposing an additional level of post-transcriptional regulation. Functionally, SNHG6 promotes tumor growth and metastasis by inducing epithelial to mesenchymal transition. Further investigations showed that SNHG6 could affect HCC tumorigenesis by binding to up-frameshift protein 1 and regulating Smad7 expression. (C) 2016 Elsevier Ireland Ltd. All rights reserved.