Dissecting the Role of Circular RNAs in Sarcomas with Emphasis on Osteosarcomas

Circular RNAs (circRNAs) are single-stranded RNAs generated from exons back-splicing from a single pre-mRNA, forming covalently closed loop structures which lack 5′-3′-polarity or polyadenylated tail. Ongoing research depicts that circRNAs play a pivotal role in tumorigenesis, tumor progression, metastatic potential and chemoresistance by regulating transcription, microRNA (miRNA) sponging, RNA-binding protein interactions, alternative splicing and to a lesser degree, protein coding. Sarcomas are rare malignant tumors stemming from mesenchymal cells. Due to their clinically insidious onset, they often present at advanced stage and their treatment may require aggressive chemotherapeutic or surgical options. This review is mainly focused on the regulatory functions of circRNAs on osteosarcoma progression and their potential role as biomarkers, an area which has prompted lately extensive research. The attributed oncogenic role of circRNAs on other mesenchymal tumors such as Kaposi Sarcoma (KS), Rhabdomyosarcoma (RMS) or Gastrointestinal Stromal Tumors (GISTs) is also described. The involvement of circRNAs on sarcoma oncogenesis and relevant emerging diagnostic, prognostic and therapeutic applications are expected to gain more research interest in the future.