Upregulation of SOX2-activated lncRNA ANRIL promotes nasopharyngeal carcinoma cell growth

Sci Rep. 2018 Feb 20;8(1):3333. doi: 10.1038/s41598-018-21708-z.

Abstract

Recent molecularly targeted approaches have gained advances in nasopharyngeal carcinoma treatment. However, the estimated five-year survival rate has not met the desired degree of improvement. Here, we report that upregulation of the expression of the SOX2-activated lncRNA ANRIL is involved in nasopharyngeal carcinoma. ANRIL has been found to be upregulated in clinical nasopharyngeal carcinoma. Using genetic approaches targeting ANRIL in nasopharyngeal carcinoma cells, we found that the knockdown of ANRIL inhibits cell proliferation in vitro and in vivo. Mechanistically, SOX2 binds with ANRIL and increases its RNA level, which upregulates β-catenin signalling, resulting in enhanced nasopharyngeal carcinoma tumourigenesis. Expression levels of ANRIL are positively correlated with SOX2 and β-catenin in clinical nasopharyngeal carcinoma samples. Our findings demonstrate that the SOX2-ANRIL-β-catenin axis plays a critical role in nasopharyngeal carcinoma proliferation and provide a potential therapeutic approach for nasopharyngeal carcinoma patients.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • CDKN2B antisense RNA, human
  • CTNNB1 protein, human
  • RNA, Long Noncoding
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • beta Catenin