Tumor-suppressive miR-218-5p inhibits cancer cell proliferation and migration via EGFR in non-small cell lung cancer

Oncotarget. 2016 May 10;7(19):28075-85. doi: 10.18632/oncotarget.8576.

Abstract

Lung cancer remains the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. Recently, microRNAs (miRNAs) have been consistently demonstrated to be involved in NSCLC and to act as either tumor oncogenes or tumor suppressors. In this study, we identified a specific binding site for miR-218-5p in the 3'-untranslated region of the epidermal growth factor receptor (EGFR). We further experimentally validated miR-218-5p as a direct regulator of EGFR. We also identified an inverse correlation between miR-218-5p and EGFR protein levels in NSCLC tissue samples. Moreover, we demonstrated that miR-218-5p plays a critical role in suppressing the proliferation and migration of lung cancer cells probably by binding to EGFR. Finally, we examined the function of miR-218-5p in vivo and revealed that miR-218-5p exerts an anti-tumor effect by negatively regulating EGFR in a xenograft mouse model. Taken together, the results of this study highlight an important role for miR-218-5p in the regulation of EGFR in NSCLC and may open new avenues for future lung cancer therapies.

Keywords: EGFR; NSCLC; miR-218-5p; migration; proliferation.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*

Substances

  • MIRN218 microRNA, human
  • MicroRNAs
  • EGFR protein, human
  • ErbB Receptors