PUBLICATION

Control of Angiogenesis via a VHL/miR-212/132 Axis

Authors
Lei, Z., Klasson, T.D., Brandt, M.M., van de Hoek, G., Logister, I., Cheng, C., Doevendans, P.A., Sluijter, J.P.G., Giles, R.H.
ID
ZDB-PUB-200426-3
Date
2020
Source
Cells   9(4): (Journal)
Registered Authors
Logister, Ive
Keywords
VHL loss of function, angiogenesis, microRNA-212/132
MeSH Terms
  • Angiogenesis Inducing Agents/metabolism
  • Carcinoma, Renal Cell/genetics
  • Carcinoma, Renal Cell/pathology
  • Cell Line, Tumor
  • Endothelial Cells/metabolism
  • Gene Expression Regulation, Neoplastic/genetics*
  • Humans
  • Kidney/pathology
  • Kidney Neoplasms/genetics
  • Kidney Neoplasms/pathology
  • MicroRNAs/genetics*
  • Up-Regulation
  • Von Hippel-Lindau Tumor Suppressor Protein/genetics*
PubMed
32325871 Full text @ Cells
Abstract
A common feature of tumorigenesis is the upregulation of angiogenesis pathways in order to supply nutrients via the blood for the growing tumor. Understanding how cells promote angiogenesis and how to control these processes pharmaceutically are of great clinical interest. Clear cell renal cell carcinoma (ccRCC) is the most common form of sporadic and inherited kidney cancer which is associated with excess neovascularization. ccRCC is highly associated with biallelic mutations in the von Hippel-Lindau (VHL) tumor suppressor gene. Although upregulation of the miR-212/132 family and disturbed VHL signaling have both been linked with angiogenesis, no evidence of a possible connection between the two has yet been made. We show that miRNA-212/132 levels are increased after loss of functional pVHL, the protein product of the VHL gene, in vivo and in vitro. Furthermore, we show that blocking miRNA-212/132 with anti-miRs can significantly alleviate the excessive vascular branching phenotype characteristic of vhl-/- mutant zebrafish. Moreover, using human umbilical vascular endothelial cells (HUVECs) and an endothelial cell/pericyte coculture system, we observed that VHL knockdown promotes endothelial cells neovascularization capacity in vitro, an effect which can be inhibited by anti-miR-212/132 treatment. Taken together, our results demonstrate an important role for miRNA-212/132 in angiogenesis induced by loss of VHL. Intriguingly, this also presents a possibility for the pharmaceutical manipulation of angiogenesis by modulating levels of MiR212/132.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes