Advancements in Understanding the Role of Circular RNA in Osteosarcoma

Osteosarcoma, the most prevalent primary malignant bone tumor and the third most frequent cancer in children and adolescents worldwide, still poses a significant therapeutic challenge. Even though combined chemotherapy and surgical resection have improved survival rates up to 60%, the prognosis for most patients with metastatic osteosarcoma continues to be dismal. The specific pathogenesis and key regulators of tumor invasion and metastasis remain largely elusive. Circular RNAs (circRNAs), novel endogenous non-coding RNA molecules that form covalently closed continuous loops through splicing, play a crucial role in the development, progression, clinical diagnosis, and treatment of various diseases. Recently, an escalating number of circular structures have been identified in osteosarcoma. Understanding their role in osteosarcoma is advantageous for early detection, diagnosis, and treatment of this disease. The primary function of circRNA involves its unique ability to bind specifically to miRNA, although their biological functions also extend to interacting with proteins, regulating gene transcription, and serving as translation templates. In this review, we explore the mechanisms and clinical applications of circRNAs in the pathogenesis and progression of osteosarcoma, with a particular emphasis on the regulatory mechanisms and functions of circRNAs as miRNA sponges in osteosarcoma development.