A Systems Biology Approach to Identify Candidate Targets to Downregulate Angiogenic Gene Expression in Cancer

Abstract

The control of angiogenesis in cancer has been recognized as a promising therapeutic target for many diseases like cancer. Specifically, the Angiopoietin-2 - Vascular Endothelial Growth Factor system has demonstrated special relevance in the regulation of angiogenesis, highlighting the importance of the complex coordination among vascular signaling molecules [3] for the identification of targets for future anti-angiogenic therapy. Current approaches to regulate the angiogenesis process focus their efforts only on VEGF regulation but this has proven ineffective in many kinds of cancer, prompting the need for further understanding of how the vasculature can be effectively targeted in tumors [9]. Given the complex properties of gene expression in this process, a Systems Biology approach is required to identify putative candidates to robustly regulate genes involved in angiogenesis. We propose a model with candidate targets to downregulate the angiogenic genes expression. We identified a strong regulation of the AKT1-ANGPT2-KDR axis by miR200B and miR200C. Also, we identified a strong regulation of SRC by miR34a. These candidate miRNAs could therefore have a potential for the development of novel therapeutic strategies against angiogenesis in cancer.