Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer

J Cell Physiol. 2019 Aug;234(10):17420-17432. doi: 10.1002/jcp.28364. Epub 2019 Feb 21.

Abstract

The function of DLEU1 in human cancer is largely unknown. The Cancer Genome Atlas data were applied to identify the landscape of differential genes between tumor tissues and normal tissues, which was further validated by our cohort data and pan-cancer data including 33 cancer types with 11,060 patients. Next, DLEU1 was selected to validate the novel finding and result showed that it promoted tumorigenesis in vitro and in vivo. Mechanistically, DLEU1 promotes SRP4 expression via increasing H3K27ac enrichment to SRP4 locus epigenetically. Moreover, epigenetic modification leads to upregulation of DLEU1 expression via decreased DNA methylation and increased H3K27ac and H3K4me3 histone modification in its locus. Finally, high expression of DLEU1 correlates with worse prognosis not only in specific cancer type patients but also in patients in the pan-cancer cohort. In summary, the work broadens the function landscape of known long noncoding RNAs in human cancer and provides novel insights into their roles in tumorigenesis.

Keywords: DLEU1; epigenetic modification; lncRNAs; prognosis; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Epigenesis, Genetic / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • RNA, Long Noncoding / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation

Substances

  • DLEU1 lncRNA, human
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins