Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans

Hepatology. 2011 Nov;54(5):1679-89. doi: 10.1002/hep.24563. Epub 2011 Sep 6.


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.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / genetics
  • DNA-Binding Proteins / genetics*
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Silencing
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Prognosis
  • RNA, Untranslated / genetics*
  • Repressor Proteins / genetics
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Polycomb-Group Proteins
  • RNA, Untranslated
  • Repressor Proteins
  • Transcription Factors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2