“School of Biological”

Back to Papers Home
Back to Papers of School of Biological

Paper   IPM / Biological / 16757
School of Biological Sciences
  Title:   Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells
1.  Hamid Latifi-Navid
2.  Zahra-Soheila Soheili
3.  Shahram Samiei
4.  Mehdi Sadeghi
5.  Sepideh Taghizadeh
6.  Ehsan Ranaei Pirmardan
7.  Hamid Ahmadieh
  Status:   Published
  Journal: Journal of Cellular and Molecular Medicine
  Year:  2021
  Supported by:  IPM
Angiogenesis, inflammation and endothelial cells’ migration and proliferation exert fundamental roles in different diseases. However, more studies are needed to identify key proteins and pathways involved in these processes. Aflibercept has received the approval of the US Food and Drug Administration (FDA) for the treatment of wet AMD and colorectal cancer. Moreover, the effect of Aflibercept on VEGFR2 downstream signalling pathways has not been investigated yet. Here, we integrated text mining data, protein-protein interaction networks and multi-experiment microarray data to specify candidate genes that are involved in VEGFA/VEGFR2 signalling pathways. Network analysis of candidate genes determined the importance of the nominated genes via different centrality parameters. Thereupon, several genes—with the highest centrality indexes—were recruited to investigate the impact of Aflibercept on their expression pattern in HUVEC cells. Real-time PCR was performed, and relative expression of the specific genes revealed that Aflibercept modulated angiogenic process by VEGF/PI3KA/AKT/mTOR axis, invasion by MMP14/MMP9 axis and inflammation-related angiogenesis by IL-6-STAT3 axis. Data showed Aflibercept simultaneously affected these processes and determined the nominated axes that had been affected by the drug. Furthermore, integrating the results of Aflibercept on expression of candidate genes with the current network analysis suggested that resistance against the Aflibercept effect is a plausible process in HUVEC cells.

Download TeX format
back to top
scroll left or right