Introduction: vUnderstanding the transcriptional regulatory networks that map out the coordinated responses of transcription factors and target genes would represent a significant advance in the analysis of osteosarcoma, a common primary bone malignancy. The objective of our study was to interpret the mechanisms of osteosarcoma through the regulation network construction.
Material and methods: Using GSE14359 datasets downloaded from Gene Expression Omnibus data, we first screened the differentially expressed genes in osteosarcoma. We explored the regulation relationship between transcription factors and target genes using Cytoscape. The underlying molecular mechanisms of these crucial target genes were investigated by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.
Results: A total of 1836 differentially expressed were identified and 98 regulatory relationships were constructed between 32 transcription factors and their 60 differentially expressed target genes. Furthermore, BCL2-like 1 (BCL2L1), tumor protein p53 (TP53), v-rel reticuloendotheliosis viral oncogene homolog A (avian) (RELA), interleukin 6 (IL6), retinoic acid receptor, alpha (RARA), nuclear factor I/C (CCAAT-binding transcription factor) (NFIC), and CCAAT/enhancer binding protein, beta (CEBPB) formed a small pivotal network, in which IL-6 could be regulated by TP53, NFIC, RARA, and CEBPB, but BCL2L1 may be only regulated by TP53 and RELA. These genes had been demonstrated to be involved in osteosarcoma progression via various biological processes and pathways, including regulation of cell apoptosis, proliferation, antigen processing and presentation pathway, and phosphatidylinositol signaling system.
Conclusions: In general, we have obtained a regulatory network and several pathways that may play important roles in osteosarcoma, identified several pivotal genes in osteosarcoma, and predicted several potential key genes for osteosarcoma.