miR-524-5p inhibits angiogenesis through targeting WNK1 in colon cancer cells

Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G827-G839. doi: 10.1152/ajpgi.00369.2019. Epub 2020 Mar 16.

Abstract

There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524-5p has been reported to possess anticancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of the miRNA-524-5p/with-no-lysine kinase 1 (WNK1) system on angiogenesis in a colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. We found miRNA-524-5p expression was relatively high in COLO205 cells and relatively low in HT-29 cells. Elevating miRNA-524-5p expression inhibited proliferation, induced cycle arrest, diminished vascular endothelial growth factor production, and thereby suppressed angiogenesis in HT-29 cells. WNK1 silencing exerted the ability of antiangiogenesis in HT-29 cells. Besides, miRNA-524-5p deficiency-induced angiogenesis was impeded by WNK1 silence in COLO205 cells. In a murine tumor model, miRNA-524-5p agomir treatment significantly suppressed colon cancer tumorigenicity with the downregulation of WNK1 expression. In summary, our results indicated that miRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting WNK1.NEW & NOTEWORTHY MiRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting with-no-lysine kinase 1.

Keywords: WNK1; angiogenesis; colon cancer; miRNA-524-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic / physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms, Experimental
  • Neovascularization, Pathologic / metabolism*
  • Up-Regulation
  • WNK Lysine-Deficient Protein Kinase 1 / genetics
  • WNK Lysine-Deficient Protein Kinase 1 / metabolism*

Substances

  • MIRN-524 microRNA, human
  • MicroRNAs
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human