Abstract
BackgroundHepatocellular 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.Methods and resultsIn 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.ConclusionOur results suggest that lncRNA TUG1, as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0431-0) contains supplementary material, which is available to authorized users.
Highlights
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood
Our results suggest that long non-coding RNAs (lncRNAs) Taurine Up-regulated Gene 1 (TUG1), as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC
TUG1 is up-regulated in hepatocellular carcinoma tissues and is associated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage The level of TUG1 was detected in 77 paired HCC tissues and corresponding adjacent normal tissues by quantitative polymerase chain reaction (qPCR), and normalized to GAPDH
Summary
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood. Hepatocellular carcinoma (HCC) is the dominant histological type of primary liver cancer which accounts for 70–85 % of primary malignancies in liver, and HCC is the third leading cause of cancer-related death worldwide [1]. While, half of these cases and deaths were estimated to occur in China [2]. A number of studies demonstrate that lncRNAs play an important role in tumorigenesis, and their misexpression confers tumor initiation, cancer cells growth and metastasis [13,14,15]. There has been a heavy focus on the ways that lncRNAs contribute to cancers development, but their aberrant expression and functional roles in HCC development and diagnosis are still not well documented
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