Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway.
Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway.
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长非编码 RNA SNHG5 通过调节 miR-26a-5p/GSK3β 信号通路促进人肝细胞癌进展
DOI：
10.1038/s41419-018-0882-5
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发表时间：
2018-08-30
影响因子：
9
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Li Y;Guo D;Zhao Y;Ren M;Lu G;Wang Y;Zhang J;Mi C;He S;Lu X
越来越多的证据表明，长的非编码RNA(LncRNAs)在人类癌症的发展中起着不正常的作用。本研究旨在利用人肝细胞癌组织和细胞系，研究lncRNA小核仁RNA宿主基因5(SNHG5)在肝细胞癌进展中的作用。实时定量聚合酶链式反应结果显示，SNHG5在肝癌组织和肝癌细胞系中均呈上调表达，且与肿瘤大小、乙肝病毒感染、组织学分级、TNM分期、门静脉癌栓(PVTT)密切相关。SNHG5基因敲除可诱导肝癌细胞发生凋亡，抑制细胞周期进程、细胞生长和转移，而SNHG5过表达则有相反的作用。在体内功能分析中，SNHG5基因敲除细胞生长的异种移植瘤的平均体积比阴性对照细胞生长的肿瘤小。进一步的研究表明，SNHG5可能通过竞争性结合miR-26a-5p，从而调节下游靶标Gsk3β的去抑制而发挥竞争内源RNA的作用，并通过荧光素酶报告实验进一步证实了这一点。在功能上，SNHG5通过激活Wnt/β-catenin途径，诱导上皮细胞向间充质转化，促进肿瘤生长和转移。总之，SNHG5通过竞争性结合miR-26a-5p，调节GSK3β和Wnt/β-catenin信号通路，促进肝癌的进展。
Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infection, histologic grade, TNM stage, and portal vein tumor thrombus (PVTT) in HCC patients. Knockdown of SNHG5 induced apoptosis and repressed cell cycle progression, cell growth, and metastasis in hepatoma cell lines, whereas overexpression of SNHG5 had the opposite effects. In vivo functional assay, xenograft tumors grown from SNHG5-knockdown cells had smaller mean volumes than the tumors grown from negative control cells. Further investigations showed that SNHG5 may act as a competing endogenous RNA by competitively binding miR-26a-5p and thereby modulating the derepression of downstream target GSK3β, which were further confirmed by luciferase reporter assay. Functionally, SNHG5 promotes tumor growth and metastasis by activating Wnt/β-catenin pathway and inducing epithelial to mesenchymal transition (EMT). Taken together, SNHG5 promotes HCC progression by competitively binding miR-26a-5p and regulating GSK3β and Wnt/β-catenin signal pathway.
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