Circular RNAs in osteosarcoma: mechanistic insights, autophagy regulation, and potential therapeutic strategies.
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Osteosarcoma (OS) represents a highly aggressive malignant neoplasm of the bone, predominantly affecting pediatric and adolescent populations. Despite significant advancements in surgical techniques and chemotherapeutic regimens, patient prognoses remain suboptimal, primarily due to elevated rates of metastasis and the development of chemoresistance. Circular RNAs (circRNAs), a class of stable and tissue-specific non-coding RNAs, have emerged as critical regulators in diverse biological processes, including autophagy-a crucial mechanism implicated in tumor progression and therapeutic resistance. This review systematically summarizes the multifaceted roles of circRNAs in the initiation and progression of osteosarcoma, with a central focus on the molecular mechanisms by which circRNAs modulate cellular proliferation, migration, invasion, metastasis, and above all, chemotherapy resistance. Special attention is given to the interaction between circRNAs and autophagy pathways (e.g., PINK1/Parkin and PI3K/AKT signaling), underscoring the dual roles of circRNAs in both facilitating tumor survival via modulating cytoprotective autophagy and inducing autophagic cell death in OS. Furthermore, the potential of circRNAs as non-invasive diagnostic biomarkers, prognostic indicators, and therapeutic targets is examined, with an emphasis on their capacity to modulate miRNA sponging and downstream signaling pathways. Despite these promising advancements, several key challenges remain in the clinical translation of circRNA-targeted strategies for OS management.