Innovative Insights into Osteosarcoma: Unraveling the Role of LncRNAs, miRNAs, and CircRNAs in Tumorigenesis and Therapeutic Resistance

Osteosarcoma (OS) is the most common form of primary bone malignancy, characterized by the production of osteoid tissue and contributing significantly to cancer-related mortality in both pediatric and adult populations. The etiology of OS remains multifactorial, involving genetic predispositions, environmental exposures, and complex molecular alterations. Despite advances in surgery and chemotherapy, therapeutic outcomes remain suboptimal due to the high propensity for metastasis and chemoresistance. This review explores recent insights into the genomic landscape of OS, with a focus on the regulatory roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in tumor initiation, progression, and therapy resistance. We further examine emerging strategies that target these non-coding RNAs as potential therapeutic agents or biomarkers for diagnosis and prognosis. Ultimately, this review emphasizes the need for innovative RNA-based approaches to improve the clinical management and survival outcomes of osteosarcoma patients.