Targeting FOS attenuates malignant phenotypes of breast cancer: Evidence from in silico and in vitro studies.

Abstract

Data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases can reveal important information behind molecular biomarkers and their associated oncogenesis. Therefore, this study was based on in silico predictions and in vitro experiments to explore regulatory network associated with breast carcinogenesis. The breast cancer (BC)-related data sets were retrieved from GEO database, followed by differential analysis and protein-protein interaction (PPI) analysis. Then, Fos proto-oncogene, AP-1 transcription factor subunit (FOS)-associated gene network was constructed, and the key gene-related genes in BC were screened by LinkedOmics. Finally, FOS expression was determined in BC tissues and cells, and gain-of-function assays were performed to define the role of FOS in BC cells. It was noted that seven differentially expressed genes (EGR1, RASSF9, FOSB, CDC20, KLF4, PTGS2, and FOS) were obtained from BC microarray data sets. FOS was the gene with the most nodes in PPI analysis. Poor FOS mRNA expression was identified in BC patients. Furthermore, FOS was mainly located in the extracellular matrix and was involved in cell processes. FOS was downregulated in BC tissues and cells, and FOS overexpression restrained the malignant phenotypes of BC cells. Collectively, ectopic expression of FOS curtails the development of BC.