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. 2020 Dec 8;10(1):21440.
doi: 10.1038/s41598-020-78574-x.

Network analysis reveals essential proteins that regulate sodium-iodide symporter expression in anaplastic thyroid carcinoma

Hassan Rakhsh-Khorshid  1   2 , Hilda Samimi  3 , Shukoofeh Torabi  4 , Sayed Mahmoud Sajjadi-Jazi  3   5 , Hamed Samadi  3 , Fatemeh Ghafouri  3   6 , Yazdan Asgari  7 , Vahid Haghpanah  8   9
Affiliations

Network analysis reveals essential proteins that regulate sodium-iodide symporter expression in anaplastic thyroid carcinoma

Hassan Rakhsh-Khorshid et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Size distribution of protein communities of NIS expression regulatory network. 7 communities were detected, and the modularity score was calculated 0.411.
Figure 2
Figure 2
Several proteins of the four signaling pathways, including MAPK (A), PI3K/AKT (B), TGFβ/SMAD (C) and TSH/TSHR (D), alongside a few transcription factors (E) with a role in the regulation of NIS expression in ATC from the list of 167 input proteins, also appeared in top-20 lists of centrality indices.
See this image and copyright information in PMC

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