Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma

Eur J Cancer. 2010 Dec;46(18):3409-16. doi: 10.1016/j.ejca.2010.07.047.

Abstract

MiRNAs are small, noncoding RNA molecules that emerge as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally related to cellular proliferation and apoptosis. In this study, we found that miR-21 is overexpressed in Laryngeal squamous cell carcinoma (LSCC) and correlated with advanced stage. Inhibition of miR-21 by antisense oligonucleotides (ASO) led to decreased protein level of Ras and profound suppression of cell proliferation and invasion. Hep-2 cells exposed to miR-21 ASO exhibited cell cycle arrest at G1 phase and increased apoptosis. Furthermore, growth of LSCC xenograft tumours was significantly suppressed by repeated injection of ASO-miR-21 lentivirus and the Ras protein expression in LSCC xenograft tumours was also downregulate by ASO-miR-21. Taken together, our data suggest that miR-21 may play an oncogenic role in the cellular processes of LSCC and represent a novel target for effective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Down-Regulation
  • Female
  • Humans
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / physiopathology
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Tumor Cells, Cultured

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Proto-Oncogene Proteins p21(ras)