Down-regulation of miR-129-5p inhibits growth and induces apoptosis in laryngeal squamous cell carcinoma by targeting APC

PLoS One. 2013 Oct 23;8(10):e77829. doi: 10.1371/journal.pone.0077829. eCollection 2013.

Abstract

miRNAs regulate gene expression and are key mediators of tumourigenesis. miR-129 has diverse effects in tumours, but its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. This article focuses on the role of miR-129-5p in LSCC. We show miR-129-5p is upregulated in primary LSCC tumours and correlated with advanced disease. Down-regulating miR-129-5p suppressed cell proliferation and migration, and caused cell cycle arrest in Hep-2 cell lines. Downregulation of miR-129-5p alone is sufficient to induce apoptosis both in vivo and in vitro. Moreover, the growth of LSCC xenograft exposed to miR-129-5p antisense oligonucleotides (ASO) in BALB/c mice was markedly inhibited. In addition, we found that miR-129-5p targeted adenomatous polyposis coli (APC) to release inhibition of Wnt signalling causing cell growth and tumourigenesis. Our results suggest miR-129-5p functions as an oncogene in LSCC by repressing APC and is a potential therapeutic target for LSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Oligonucleotides, Antisense / genetics

Substances

  • Adenomatous Polyposis Coli Protein
  • MicroRNAs
  • Mirn129 microRNA, human
  • Oligonucleotides, Antisense

Grants and funding

This work was supported by grants from the National Science Foundation of China (81241085); the Key Project of Natural Science Foundation of Heilongjiang Province (ZD201215/H1302); the Research Fund for the Doctoral Program of Higher Education of China (20102307110007); the Science and Technology Innovation Talent Research Funds of Harbin (2012RFXXS072); and the Postdoctoral Science Foundation of Heilongjiang Province (LBH-Z11087). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.