Long noncoding RNA uc.338 promotes cell proliferation through association with BMI1 in hepatocellular carcinoma

Hum Cell. 2016 Oct;29(4):141-7. doi: 10.1007/s13577-016-0140-z. Epub 2016 May 6.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common human cancers all over the world. Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in malignant transformation, tumor growth and metastasis in HCC. Among lncRNAs, ultraconserved RNAs (ucRNAs) containing an ultraconserved region have been report to contribute to human cancers. lncRNA ultraconserved element 338 (uc.338) was first found to be upregulated in HCC and promote cell growth. However, the exact mechanism by which uc.338 modulates cell growth remains unclear. In the present study, we demonstrated that uc.338 promotes HCC cell proliferation and induces cell cycle progression. RNA-immunoprecipitation and RNA pull-down assays showed that uc.338 associated with BMI1. We found that uc.338 promotes HCC cell proliferation and induces cell cycle progression through association with BMI1. uc.338 also modulated the transcription of CDKN1A. The oncogenic activity of uc.338 is partially due to its repression of p21. uc.338 may be a potential target for HCC therapy.

Keywords: BMI1; H2AK119ub1; PRC1; PRC2; RING1A; RING1B; lncRNA; p21; ucRNA.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Polycomb Repressive Complex 1*
  • RNA, Long Noncoding / physiology*
  • Tumor Cells, Cultured

Substances

  • BMI1 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • Polycomb Repressive Complex 1