miR-140 suppresses tumor growth and metastasis of non-small cell lung cancer by targeting insulin-like growth factor 1 receptor

PLoS One. 2013 Sep 10;8(9):e73604. doi: 10.1371/journal.pone.0073604. eCollection 2013.

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. In this study, we investigated the roles and mechanisms of miR-140 in human non-small cell lung cancer (NSCLC). We found that miR-140 is significantly downregulated in NSCLC tissues and cell lines. Both gain-of-function and loss-of-function studies demonstrated that miR-140 suppresses NSCLC cell proliferation, migration, and invasion in vitro. Importantly, overexpression of miR-140 effectively repressed tumor growth and metastasis in nude mouse models. Integrated analysis identified IGF1R as a direct and functional target of miR-140. Knockdown of IGF1R inhibited cell proliferation and invasion resembling that of miR-140 overexpression, while overexpression of IGF1R attenuated the function of miR-140 in NSCLC cells. Together, our results highlight the significance of miR-140 and IGF1R in the development and progression of NSCLC.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Burden / genetics
  • Xenograft Model Antitumor Assays / methods

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Mirn140 microRNA, human
  • Receptor, IGF Type 1

Grants and funding

The authors have no funding or support to report.