miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer

Oncotarget. 2015 Jan 30;6(3):1605-17. doi: 10.18632/oncotarget.2748.

Abstract

MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression or degradation. Our previous studies indicated that miR-874 played a suppressive role in gastric cancer (GC) development and progression. However, the role of miR-874 in tumor angiogenesis and the mechanisms underlying its function in GC remained to be clarified. Here, gain- and loss-of-function assays demonstrated that miR-874 inhibited the tumor angiogenesis of GC cells in vitro and in vivo. Through reporter gene and western blot assays, STAT3 was shown to be a direct target of miR-874. Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by miR-874. Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis caused by the miR-874-inhibitor. Furthermore, the levels of miR-874 were inversely correlated with those of STAT3 protein in GC tissues. Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Down-Regulation
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN874 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A