Current Insights into Signature MicroRNA Networks and Signal Transduction in Osteosarcoma

Osteosarcoma is one of the most common types of primary bone tumors that mainly occurs in children and adolescents. It is characterized by the development of immature bones or osteoid tissue by the tumor cells. Osteosarcoma is also often caused by metastatic tumors, and has a high global incidence. Treatment strategies are limited by the intractable nature of the disease and the likelihood for metastasis.

MicroRNAs (miRNAs) are a class of noncoding RNAs composed of 18–24 nucleotides that are major components for various biological processes like cell differentiation, cell growth, and cell death. Dysregulation of miRNAs in cells leads to altered gene expression leading to several phenotypic and genotypic changes in cells which initiate and promote carcinogenesis. Several miRNAs are involved in the pathogenesis of osteosarcoma thereby affecting the prognosis for the patient. These miRNAs, when altered, have the ability to function either as oncogenes or as tumor suppressor genes. We discuss osteosarcoma in the light of dysregulated miRNA signature networks and their biomarker targets and the delineation of miRNA-target interactions in osteosarcoma. We also elucidate key signal transduction pathways that are modulated by miRNAs in osteosarcoma. Further, we summarize dysregulated osteosarcoma miRNAs that play key role(s) in other pediatric tumors.

Taken together, we present an overview of the architecture of signature miRNA networks in osteosarcoma and provide a mechanistic basis to augment our understanding of miRNA regulation in osteosarcoma.