MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer

Cancer Gene Ther. 2017 Sep;24(9):386-392. doi: 10.1038/cgt.2017.30. Epub 2017 Jul 28.

Abstract

MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis. MiR-140-5p mimics and a negative control were transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used to detect the invasive ability of the cells, and the angiogenic ability was assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF-A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot analysis in vivo. VEGF-A was verified as a possible target gene of miR-140-5p, and corroborated by dual-luciferase reporter and ELISA. Taken together, the study elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer metastasis and angiogenesis, and provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for breast cancer patients.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Regulation*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • Neoplasm Proteins
  • RNA, Neoplasm
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A