TY - JOUR
T1 - Network analysis reveals essential proteins that regulate sodium-iodide symporter expression in anaplastic thyroid carcinoma
AU - Rakhsh-Khorshid, Hassan
AU - Samimi, Hilda
AU - Torabi, Shukoofeh
AU - Sajjadi-Jazi, Sayed Mahmoud
AU - Samadi, Hamed
AU - Ghafouri, Fatemeh
AU - Asgari, Yazdan
AU - Haghpanah, Vahid
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Anaplastic thyroid carcinoma (ATC) is the most rare and lethal form of thyroid cancer and requires effective treatment. Efforts have been made to restore sodium-iodide symporter (NIS) expression in ATC cells where it has been downregulated, yet without complete success. Systems biology approaches have been used to simplify complex biological networks. Here, we attempt to find more suitable targets in order to restore NIS expression in ATC cells. We have built a simplified protein interaction network including transcription factors and proteins involved in MAPK, TGFβ/SMAD, PI3K/AKT, and TSHR signaling pathways which regulate NIS expression, alongside proteins interacting with them. The network was analyzed, and proteins were ranked based on several centrality indices. Our results suggest that the protein interaction network of NIS expression regulation is modular, and distance-based and information-flow-based centrality indices may be better predictors of important proteins in such networks. We propose that the high-ranked proteins found in our analysis are expected to be more promising targets in attempts to restore NIS expression in ATC cells.
AB - Anaplastic thyroid carcinoma (ATC) is the most rare and lethal form of thyroid cancer and requires effective treatment. Efforts have been made to restore sodium-iodide symporter (NIS) expression in ATC cells where it has been downregulated, yet without complete success. Systems biology approaches have been used to simplify complex biological networks. Here, we attempt to find more suitable targets in order to restore NIS expression in ATC cells. We have built a simplified protein interaction network including transcription factors and proteins involved in MAPK, TGFβ/SMAD, PI3K/AKT, and TSHR signaling pathways which regulate NIS expression, alongside proteins interacting with them. The network was analyzed, and proteins were ranked based on several centrality indices. Our results suggest that the protein interaction network of NIS expression regulation is modular, and distance-based and information-flow-based centrality indices may be better predictors of important proteins in such networks. We propose that the high-ranked proteins found in our analysis are expected to be more promising targets in attempts to restore NIS expression in ATC cells.
UR - http://www.scopus.com/inward/record.url?scp=85097296054&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-78574-x
DO - 10.1038/s41598-020-78574-x
M3 - Article
C2 - 33293661
AN - SCOPUS:85097296054
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 21440
ER -