MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1

Cell Death Dis. 2014 Mar 27;5(3):e1144. doi: 10.1038/cddis.2014.110.

Abstract

The microRNAs 19a and 19b, hereafter collectively referred to as miR-19a/b, were recognised to be the most important miRNAs in the oncomiRs-miR-17-92 cluster. However, the exact roles of miR-19a/b in cancers have not been elucidated. In the present study, miR-19a/b was found to be over-expressed in gastric cancer tissues and significantly associated with the patients' metastasis of gastric cancer. Using gain or loss-of-function in in vitro and in vivo experiments, a pro-metastatic function of miR-19a/b was observed in gastric cancer. Furthermore, reporter gene assay and western blot showed that MXD1 is a direct target of miR-19a/b. Functional assays showed that not only MXD1 had an opposite effect to miR-19a/b in the regulation of gastric cancer cells, but also overexpression of MXD1 reduced both miR-19a/b and c-Myc levels, indicating a potential positive feedback loop among miR-19a/b, MXD1 and c-Myc. In conclusion, miR-17-92 cluster members miR-19a/b facilitated gastric cancer cell migration, invasion and metastasis through targeting the antagonist of c-Myc -- MXD1, implicating a novel mechanism for the malignant phenotypes of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lentivirus / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phenotype
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MIRN19 microRNA, human
  • MXD1 protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • Repressor Proteins