Deciphering lncRNA and circRNA control of autophagy in osteosarcoma mechanisms and clinical translation

Osteosarcoma (OS) is the most common aggressive bone cancer, which predominantly affects children and adolescents. It has high metastatic potential and poor survival in advanced stages. Despite the advancements in multimodal therapy, drug resistance and recurrence remain daunting. Autophagy plays a dual role in OS development-suppressing early tumorigenesis but facilitating the survival of tumor cells under stress. These include major regulators such as non-coding RNAs (ncRNAs), specifically long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These ncRNAs regulate autophagy through binding to microRNAs and modulating related signaling pathways. Their dysregulation contributes to OS cell proliferation, metastasis, immune evasion, and chemoresistance. This review summarizes current knowledge on the regulation of autophagy by lncRNAs and circRNAs in OS development. Some are oncogenic drivers that induce autophagy and drug resistance, and others are tumor suppressors that inhibit autophagy and increase drug sensitivity. Some regulatory axes, lncRNA MEG3/miR-21-5p/p53, OIP5-AS1/miR-153/ATG5, Sox2OT-V7/miR-142/miR-22, and circMRPS35/FOXO3, illustrate the complex manner in which ncRNAs affect autophagy and treatment response. Clarification of these networks enlightens OS biology and indicates ncRNAs as potential diagnostic, prognostic, and therapeutic targets.