Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.
Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.
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DOI：
10.1186/s12943-015-0431-0
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发表时间：
2015-09-04
期刊：
影响因子：
37.3
通讯作者：
Shu YQ
中科院分区：
文献类型：
--
作者：
Huang MD;Chen WM;Qi FZ;Sun M;Xu TP;Ma P;Shu YQ
肝细胞癌是世界范围内与癌症相关的死亡的主要原因之一，其生物学机制仍然知之甚少。最近的证据表明，长的非编码RNA(LncRNAs)在包括肝癌在内的多种癌症中被发现表达失调。牛磺酸上调基因1(TUG1)是一个7.1kb的lncRNA，与多梳抑制复合体2(PRC2)结合，在非小细胞肺癌(NSCLC)和食管鳞癌(ESCC)中表达缺失。然而，其临床意义和在肝细胞癌中的潜在作用仍不清楚。本研究采用定量聚合酶链式反应(QPCR)技术检测了77例肝细胞癌组织和配对的正常肝组织中TUG1的表达。TUG1在肝细胞癌组织中表达上调，且与肿瘤大小和巴塞罗那临床肝癌(BCLC)分期显著相关。此外，沉默TUG1的表达抑制了肝癌细胞的增殖、集落形成、致瘤性和诱导肝癌细胞系的凋亡。我们还发现，TUG1的过度表达是由核转录因子SP1诱导的，并且TUG1可以通过与PRC2结合并将其募集到KLF2启动子区域来表观遗传地抑制Kruppel样因子2(KLF2)的转录。我们的结果表明，作为一种生长调节因子，lncRNA TUG1可能成为一种新的肝癌诊断生物标志物和治疗靶点。本文的在线版本(doi：10.1186/s12943-0150431-0)包含补充材料，授权用户可以使用。
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood. Recent evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including HCC. Taurine Up-regulated Gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is found to be disregulated in non-small cell lung carcinoma (NSCLC) and esophageal squamous cell carcinoma (ESCC). However, its clinical significance and potential role in HCC remain unclear. In this study, expression of TUG1 was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qPCR). TUG1 expression was up-regulated in HCC tissues and the higher expression of TUG1 was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, silencing of TUG1 expression inhibited HCC cell proliferation, colony formation, tumorigenicity and induced apoptosis in HCC cell lines. We also found that TUG1 overexpression was induced by nuclear transcription factor SP1 and TUG1 could epigeneticly repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. Our results suggest that lncRNA TUG1, as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC. The online version of this article (doi:10.1186/s12943-015-0431-0) contains supplementary material, which is available to authorized users.