MicroRNA-107, an oncogene microRNA that regulates tumour invasion and metastasis by targeting DICER1 in gastric cancer

J Cell Mol Med. 2011 Sep;15(9):1887-95. doi: 10.1111/j.1582-4934.2010.01194.x.

Abstract

MicroRNAs are small non-coding RNA molecules that control expression of target genes. Previous studies showed that microRNA-107 (miR-107) is overexpressed in gastric cancer tissues compared with the matched normal tissues. However, it remains largely unclear as to how miR-107 exerts its function and modulates the malignant phenotypes of gastric cancer, because our understanding of miR-107 signalling pathways is limited. In this study, we demonstrate that miR-107 is frequently up-regulated in gastric cancers and its overexpression is significantly associated with gastric cancer metastasis. Furthermore, silencing the expression of miR-107 could inhibit gastric cancer cell migration and invasion in vitro and in vivo. Subsequent investigation characterized DICER1 as a direct target of miR-107. Up-regulation of DICER1 resulted in a dramatic reduction of in vitro migration, invasion, in vivo liver metastasis of nude mice, which is similar to that occurs with the silencing of miR-107, indicating that DICER1 functions as a metastasis suppressor in gastric cancer. Furthermore, the restoration of DICER1 can inhibit miR-107-induced gastric cancer cell invasion and metastasis. In conclusion, our results suggested that miR-107, an oncogene miRNA promoting gastric cancer metastasis through down-regulation of DICER1. Inhibition of miR-107 or restoration of DICER1 may represent a new potential therapeutic target for gastric cancer treatment.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cell Movement / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Down-Regulation / genetics
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Oncogenes / genetics*
  • Phenotype
  • Prognosis
  • Ribonuclease III / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Transcription, Genetic
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • MIRN107 microRNA, human
  • MicroRNAs
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases