Direct targeting of HGF by miR-16 regulates proliferation and migration in gastric cancer

Tumour Biol. 2016 Nov;37(11):15175-15183. doi: 10.1007/s13277-016-5390-6. Epub 2016 Sep 28.

Abstract

MicroRNAs (miRNAs) have been reported to be involved in each stage of tumor development in various types of cancers. We have previously showed that miR-16 is downregulated in cancer and acts as a tumor suppressor. Other studies indicated that hepatocyte growth factor (HGF)/c-Met is implicated in proliferation, migration, and other pathophysiological processes. However, little is known about the relationship between miR-16 and HGF/c-Met in gastric cancer (GC). In the present study, we used bioinformatics tools and related experiments to search for miRNAs targeting HGF. Here, we found that miR-16 suppressed HGF protein expression by directly targeting 3'-untranslated region (UTR) of HGF mRNA. Subsequently, it was illustrated the downregulation of miR-16 promotes, while overexpressed of miR-16 significantly inhibits cell proliferation and migration by negatively regulating HGF/c-Met pathway. Moreover, the biological role of HGF in GC cells was determined by using HGF siRNA and HGF-overexpressing plasmid, respectively. To conclude, our results provide a potential target by using miR-16 for the future clinical treatment of GC.

Keywords: GC; HGF; Migration; Proliferation; miR-16.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Case-Control Studies
  • Cell Movement*
  • Cell Proliferation*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Hepatocyte Growth Factor