miR-622 inhibits angiogenesis by suppressing the CXCR4-VEGFA axis in colorectal cancer

Gene. 2019 May 30:699:37-42. doi: 10.1016/j.gene.2019.03.004. Epub 2019 Mar 6.

Abstract

Angiogenesis is essential for tumor metastasis. Our previous study has revealed that miR-622 inhibits colorectal cancer (CRC) metastasis. Here, we aimed to explore the effects and potential molecular mechanisms of action of miR-622 on angiogenesis. We found that overexpression of miR-622 inhibited CRC angiogenesis in vitro, according to suppression of proliferation, migration, tube formation, and invasiveness of human umbilical vein endothelial cells (HUVECs) treated with a tumor cell-conditioned medium derived from Caco-2 or HT-29 cells. Likewise, enhanced miR-622 expression suppressed CRC angiogenesis in vivo as determined by the measurement of Ki67 and VEGFA levels and microvessel density (by immunostaining). CXCR4, encoding a positive regulator of vascular endothelial growth factor A (VEGFA), was shown to be a direct target of miR-622. Overexpression of CXCR4 attenuated the inhibition of VEGFA expression by miR-622 and reversed the loss of tumor angiogenesis caused by miR-622. Taken together, these data show that miR-622 inhibits CRC angiogenesis by suppressing the CXCR4-VEGFA signaling axis, which represents a promising target for developing a new therapeutic strategy against CRC.

Keywords: Angiogenesis; CXCR4; Colorectal cancer; VEGFA; miR-622.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • HT29 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Receptors, CXCR4 / genetics*
  • Signal Transduction / genetics
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • CXCR4 protein, human
  • MIRN622 microRNA, human
  • MicroRNAs
  • Receptors, CXCR4
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A