miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer

Cell Physiol Biochem. 2013;32(1):64-73. doi: 10.1159/000350125. Epub 2013 Jul 4.

Abstract

Background/aims: MicroRNA (miRNA) plays important roles in the development of different cancers. In this study, we investigated the roles and mechanisms of miR-203 in human cervical cancer.

Methods: miR-203 expression was detected in cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the promoter region of miR-203 was examined by methylation-specific PCR. The functional effect of miR-203 was determined by both in vitro and in vivo assays.

Results: miR-203 was frequently down-regulated in cervical cancer tumors and cell lines. This down-regulation of miR-203 was associated with methylation of the miR-203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth factor alpha (VEGFA) expression by directly targeting its 3'-untranslated region. Functional assays revealed that miR-203 suppressed cervical cancer cell proliferation, tumor growth, and angiogenesis in nude mice, whereas forced expression of VEGFA rescued this inhibitory effect.

Conclusion: Our collective findings indicate that miR-203 functions as a tumor suppressor by targeting VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR-203 may be a potential therapeutic target and prognostic marker in cervical cancer.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • Down-Regulation
  • Female
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic
  • Promoter Regions, Genetic
  • Transplantation, Heterologous
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN203 microRNA, human
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A