Premium
Systems toxicology assessment revealed the impact of graphene‐based materials on cell cycle regulators
Author(s) -
Farahani Masoumeh,
RezaeiTavirani Mostafa,
Zali Hakimeh,
Hatamie Shadie,
Ghasemi Nazanin
Publication year - 2020
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36923
Subject(s) - cell cycle , graphene , gene expression , gene , cyclin dependent kinase 1 , computational biology , cell cycle checkpoint , betweenness centrality , biology , microbiology and biotechnology , materials science , nanotechnology , genetics , centrality , mathematics , combinatorics
Understanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene‐exposed cells was retrieved from the Gene expression omnibus database. Differentially expressed genes and their functional roles were then investigated through the pathway, protein–protein interaction (PPI) network, and module analysis. High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene–gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub–bottleneck genes in graphene‐treated murine peritoneal macrophages and human breast cancer cell line by real‐time PCR. The five hub–bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene–cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene‐based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine.