Long non-coding RNA AWPPH enhances malignant phenotypes in nasopharyngeal carcinoma via silencing PTEN through interacting with LSD1 and EZH2

Biochem Cell Biol. 2021 Apr;99(2):195-202. doi: 10.1139/bcb-2019-0497. Epub 2020 Jul 14.

Abstract

Evidence has emerged identifying long noncoding RNAs (lncRNAs) as important regulators of various cancers including nasopharyngeal carcinoma (NPC). LncRNA AWPPH is an oncogene recently identified in several cancers. However, the underlying role of AWPPH in NPC is still unclear and thus worth exploring. In this study, AWPPH expression was markedly upregulated in NPC cells. Further, loss- and gain-of-function assays indicated that AWPPH facilitates cell proliferation and migration and hinders apoptosis in NPC cells. Moreover, cytoplasmic AWPPH was predicted to share a common RNA-binding protein, IGF2BP1, with LSD1. The interaction between IGF2BP1 and both AWPPH and LSD1 mRNA was verified in NPC cells, and AWPPH stabilized LSD1 mRNA to enhance the expression of LSD1 in NPC through such interactions. Furthermore, nuclear AWPPH repressed PTEN expression through recruiting EZH2 and LSD1 to the PTEN promoter in NPC cells. Final rescue assays demonstrated that silenced PTEN could reverse the suppressive influence of AWPPH depletion on the progression of NPC. Collectively, our study shows that AWPPH inhibits PTEN expression to drive NPC progression through interacting with LSD1 and EZH2, providing potential biomarkers for NPC treatment.

Keywords: AWPPH; CNP; EZH2; LSD1; NPC; PTEN.

MeSH terms

  • Apoptosis
  • Cell Survival
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Gene Silencing
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Nasopharyngeal Carcinoma / genetics*
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phenotype
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Cells, Cultured

Substances

  • RNA, Long Noncoding
  • Histone Demethylases
  • KDM1A protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • PTEN Phosphohydrolase
  • PTEN protein, human