Open AccessNetwork analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells
Author(s) -
LatifiNavid Hamid,
Soheili ZahraSoheila,
Samiei Shahram,
Sadeghi Mehdi,
Taghizadeh Sepideh,
Pirmardan Ehsan Ranaei,
Ahmadieh Hamid
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16778
Subject(s) - aflibercept , angiogenesis , biology , vascular endothelial growth factor a , pi3k/akt/mtor pathway , cancer research , computational biology , signal transduction , vascular endothelial growth factor , microbiology and biotechnology , genetics , vegf receptors , bevacizumab , chemotherapy
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.