LincRNA-ROR is activated by H3K27 acetylation and induces EMT in retinoblastoma by acting as a sponge of miR-32 to activate the Notch signaling pathway

Cancer Gene Ther. 2021 Feb;28(1-2):42-54. doi: 10.1038/s41417-020-0181-z. Epub 2020 May 22.


Recent studies have suggested that lincRNA-ROR is involved in the tumorigenesis of different types of cancers. However, the role of lincRNA-ROR in retinoblastoma has not been determined. We investigated lincRNA-ROR levels in 58 retinoblastoma and adjacent non-tumor tissues by quantitative reverse transcription PCR. Recurrence-free survival was analyzed using Cox regression analyses. Cell migration and invasion abilities were detected by wound-healing, Transwell invasion, and bioluminescence imaging assays. Western blotting was performed to detect epithelial-mesenchymal transition markers. Interactions between lincRNA-ROR, miR-32-5p, and Notch1 were confirmed by Luciferase, RNA pull-down, and RIP assays. Histone acetylation was detected by chromatin immunoprecipitation assays. We showed that lincRNA-ROR was significantly upregulated in retinoblastoma tissues, and overexpression of lincRNA-ROR was significantly correlated with optic nerve invasion, nodal or distant metastasis, and recurrence. We also showed that lincRNA-ROR is a critical promoter of retinoblastoma cell metastasis, both in vivo and in vitro. Further, we demonstrated that lincRNA-ROR activates the Notch signaling pathway by acting as a sponge of miR-32-5p. Upregulation of lincRNA-ROR was attributed to the CBP-mediated H3K27 acetylation at the promoter region. Our results reveal a potential competing endogenous RNA regulatory pathway, in which lincRNA-ROR modulates the epithelial-mesenchymal transition program by competitively binding to endogenous miR-32-5p and regulating Notch signaling pathway activity in retinoblastoma cells, which may provide new insights into novel molecular therapeutic targets for retinoblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Humans
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Retinoblastoma / genetics*
  • Retinoblastoma / mortality
  • Signal Transduction
  • Survival Analysis
  • Transfection


  • MIRN32 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding