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Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans
Author(s) -
Yang Fu,
Zhang Ling,
Huo Xisong,
Yuan Jihang,
Xu Dan,
Yuan Shengxian,
Zhu Nan,
Zhou Weiping,
Yang Guangshun,
Wang Yuzhao,
Shang Jingli,
Gao Chunfang,
Zhang Fengrui,
Wang Fang,
Sun Shuhan
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24563
Subject(s) - hepatocellular carcinoma , long non coding rna , ezh2 , biology , cancer research , gene silencing , enhancer , hepatology , meg3 , hepatitis b virus , microarray , gene expression , rna , gene , medicine , virology , genetics , virus
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of lncRNAs to hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) remain largely unknown. Differentially expressed lncRNAs between HBV‐related HCC and paired peritumoral tissues were identified by microarray and validated using quantitative real‐time polymerase chain reaction. Liver samples from patients with HBV‐related HCC were analyzed for levels of a specific differentially expressed lncRNA High Expression In HCC (termed lncRNA‐HEIH); data were compared with survival data using the Kaplan‐Meier method and compared between groups by the log‐rank test. The effects of lncRNA‐HEIH were assessed by silencing and overexpressing the lncRNA in vitro and in vivo . The expression level of lncRNA‐HEIH in HBV‐related HCC is significantly associated with recurrence and is an independent prognostic factor for survival. We also found that lncRNA‐HEIH plays a key role in G 0 /G 1 arrest, and further demonstrated that lncRNA‐HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Conclusions: Together, these results indicate that lncRNA‐HEIH is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in HCC progression. (H EPATOLOGY 2011