Identification and Analysis of Transcriptional Regulatory Networks of Osteosarcoma Microarray Data via Systems Biology

Abstract

Osteosarcoma is a relatively uncommon tumor that is defined histologically by malignant cells developing osteoid. Osteosarcomas are mesenchymal cell tumors that cause abnormal bone growth. A combination of genetic, epigenetic, and environmental factors leads mesenchymal stem cells to develop into bone precursor cells, resulting in osteosarcoma. Only tumor suppressor genes, such as p53, Rb, RECQL4, BLM, and WRN, have been detected in inherited family illnesses with an OS susceptibility. These genes, in particular, play an essential role in the development of OS in individuals. In this research, core genes responsible for OS were determined using a microarray and systems biology. 234 genes encoding overexpression and down-regulation were identified, among which 60 were considered as key genes, many of which had known roles in bone growth. Transcriptional regulatory networks were developed with this data and subsequently partitioned to define cis-regulatory modules. Results indicate that several OS-specific genes have strongly conserved the clustering of bone-related cis-regulatory modules, thus promoting the hypothesis that a bone-related gene network is essential for understanding OS biology and may play a role in bone contractility and anomalies.

graphical abstract