我们已发现长链非编码RNA（lncRNA）在肝癌发生、发展中发挥重要调控功能（Gastroenterology，2015）。近来，我们预实验结果表明：lncRNA SNHG6在肝癌中高表达且与患者预后不良密切相关；SNHG6可促进肝癌细胞增殖、抑制凋亡；SNHG6可作为miR-26a/b的“海绵”发挥生物学功能。基于前期研究结果，我们提出SNHG6作为竞争性内源RNA（ceRNA）发挥癌基因作用的科学假说。为验证假说，本项目将利用临床多中心、大样本分析SNHG6与肝癌发生发展的关系；其次，筛选SNHG6调控的mRNA，并阐明SNHG6－miR-26a/b－靶mRNA之间互为调控的网络关系，并通过肿瘤体内外实验及转基因动物验证SNHG6的ceRNA网络；最后，探讨SNHG6二级结构与生物学功能的关系。据此，阐明SNHG6在肝癌中确切的生物学功能及调控机制。

We have demonstrated that the expression of long noncoding RNAs (lncRNAs) has been dysregulated in hepatocellular carcinoma (HCC) and may serve as novel prognostic markers and therapeutic targets (Gastroenterology，2015). Recently, our preliminary data showed that lncRNA SNHG6 was highly expressed in HCC tissues compared with controls and was associated with portal vein tumor thrombus, tumor stage, metastasis, and shorter overall survival of HCC patients. Ectopic expression of SNHG6 in HCC cells promoted cell proliferation and inhibited apoptosis. Furthermore, SNHG6 could become a sponge for miR-26a/b. Thus, based on our data, we proposed that SNHG6 may be functioned as competing endogenous RNA (ceRNA) to promote HCC progression. To confirm the hypothesis, firstly, the effect of SNHG6 will be identified by clinical multicenter sample in HCC. Secondly, we will screen the target mRNA and explore the relationship among SNHG6, miR-26a/b, and target mRNA. Lastly, we will investigate the functions of ceRNA network involving SNHG6 by in vitro and in vivo tumor assays and SNHG6 transgene mice. In conclusion, SNHG6 may act as a biomarker for poor prognosis in HCC and confer a malignant phenotype to tumor cells. The ceRNA network involving SNHG6 may contribute to a better understanding of liver carcinogenesis and tumor progression.