Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
Our results suggest that lncRNA TUG1, as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC.
Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, Jiangsu Province, 223301, People's Republic of China.
Ming-De
MD
Huang
Department of Oncology, Jining No.1 People's Hospital, No.6, Jiankang Road, Jining City, Shandong Province, 272011, People's Republic of China.
Wen-Ming
WM
Chen
Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, Jiangsu Province, 223300, People's Republic of China.
Fu-Zhen
FZ
Qi
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
Ming
M
Sun
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
Tong-Peng
TP
Xu
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
Pei
P
Ma
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China. yongqian_shu@163.com.
Yong-Qian
YQ
Shu
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D063185:Epigenetic Repression / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics
C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding; C000598536:TUG1 long noncoding RNA, human; D063151:Polycomb Repressive Complex 2