Upregulation of long noncoding RNA TUG1 by EGR1 promotes adenomyotic epithelial cell migration and invasion through recruiting EZH2 and suppressing TIMP2

Mol Reprod Dev. 2019 Feb;86(2):239-247. doi: 10.1002/mrd.23099. Epub 2019 Jan 13.

Abstract

Emerging studies showed that lncRNA taurine upregulated 1 (TUG1) plays important roles in diverse biological processes. However, there is no previously published research reporting the regulatory role of lncRNAs in the progression of adenomyosis. In the present study, we found that TUG1 is upregulated in human adenomyosis, and the overexpression of TUG1 is associated with the transcription factor early growth response 1 (EGR1). Functionally, the knockdown of TUG1 inhibited adenomyotic epithelial cell migration and invasion but not growth. The mechanistic experiments demonstrated that the function of TUG1 in adenomyotic epithelial cell invasion is, at least in part, through recruiting the enhancer of zeste homolog 2 (EZH2) to the promoter of tissue inhibitor of metalloproteinases 2 (TIMP2) and negatively regulating its expression. Our study demonstrated that TUG1 promotes the migration and invasion of human adenomyotic epithelial cells, and EGR1/TUG1/EZH2/TIMP2 may be a potential therapeutic target for adenomyosis.

Keywords: EGR1; EZH2; TIMP2; TUG1; adenomyosis; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomyosis / metabolism*
  • Adenomyosis / pathology
  • Cell Movement*
  • Cell Proliferation*
  • Early Growth Response Protein 1 / metabolism*
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • RNA, Long Noncoding / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Up-Regulation*

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • RNA, Long Noncoding
  • TIMP2 protein, human
  • TUG1 long noncoding RNA, human
  • Tissue Inhibitor of Metalloproteinase-2
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein