Long noncoding RNA SOX2-OT facilitates laryngeal squamous cell carcinoma development by epigenetically inhibiting PTEN via methyltransferase EZH2

IUBMB Life. 2019 Sep;71(9):1230-1239. doi: 10.1002/iub.2026. Epub 2019 Feb 27.

Abstract

Long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of various cancers, including laryngeal squamous cell carcinoma (LSCC). Recently, lncRNA Sox2 overlapping transcript (SOX2-OT) has been identified as an oncogene in various cancers. However, the functional role and the regulatory mechanism of SOX2-OT in LSCC remains unclear. In this study, we found that SOX2-OT expression was increased and negatively correlated with PTEN expression in LSCC tissues. Furthermore, SOX2-OT overexpression promoted LSCC cell proliferation, migration, invasion, and suppressed cell apoptosis in vitro, as well as facilitated the in vivo tumorigenicity. By contrast, SOX2-OT silencing exerted the opposite effect. Mechanically, SOX2-OT interacted with EZH2 and recruited EZH2 to induce H3K27me3 and epigenetically inhibited PTEN expression in LSCC cells. Additionally, EZH2 silencing and PTEN overexpression significantly abrogated the SOX2-OT overexpression-mediated promotion of LSCC cell malignant behavior. Collectively, our findings demonstrate that SOX2-OT inhibits PTEN expression to facilitate LSCC development through EZH2-mediated H3K27me3. © 2019 IUBMB Life, 71(9):1230-1239, 2019.

Keywords: EZH2; H3K27me3; PTEN; SOX2-OT; laryngeal squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Epigenesis, Genetic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • Mice
  • PTEN Phosphohydrolase / genetics*
  • RNA, Long Noncoding / genetics
  • Transplantation, Heterologous

Substances

  • RNA, Long Noncoding
  • Jumonji Domain-Containing Histone Demethylases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • PTEN Phosphohydrolase
  • PTEN protein, human