Mycophenolic acid treatment alters gene regulatory network of gastric cancer cell line AGS

Mycophenolic acid, as an uncompetitive inhibitor of inosine monophosphate dehydrogenase, is used to prevent graft rejection. It has been shown that mycophenolic acid blocks T and B lymphocyte proliferation and clonal expansion. Inhibitory effects of this drug on cancer cell lines has been detected in several studies. In here, we analyzed gene regulatory network of AGS (gastric cancer cell line) following treatment with mycophenolic acid. In order to do this, we used GSE46671 dataset which is freely available on the NCBI database. Dataset were analyzed using GEO2R to determine significantly (p-value less than 0.05) differentially expressed genes in mycophenolic acid treated cells against control. Threshold for choosing the genes were ±0.6 of log2 Fold change. Then, we detected transcription factors of differentially expressed genes using ChEA and ENCODE databases. Network of differentially expressed transcription factors were constructed and analyzed using Cytoscape 3.4.0 and Gephi 0.9.1 softwares. The results shown that there are 28 differentially expressed transcription factors. Centrality analysis for detecting core gene regulatory network revealed that EGR1, SOX2, and ATF3 are main transcription factors which control promoter of other transcription factors. Following mycophenolic acid treatment, 17 of transcription factors were down-regulated while 11 were up-regulated. In here, we determined core gene regulatory network in AGS cell line treated with mycophenolic acid using systems biology. These information can help to decipher mechanisms underlying using immunosuppressive drugs against cancer.

کلیدواژه ها:

transcription factors ، gene regulatory network ، systems biology