Potential Role of RORA in Osteosarcoma Pathogenesis: Evidence from Competing Endogenous RNA Network Analysis

Background: Osteosarcoma is a relatively rare malignant tumor characterized by high aggressiveness and poor prognosis. Traditional diagnostic approaches have several limitations, particularly in early detection and disease monitoring. In recent years, exosome-derived RNAs have attracted increasing attention in cancer research because of their potential relevance to intercellular communication and tumor-related molecular alterations. However, the molecular characteristics associated with plasma exosomal RNAs in osteosarcoma remain poorly understood. Methods: In this study, RNA expression in plasma exosomes from osteosarcoma patients was investigated using differential expression, enrichment, immune infiltration, and competing endogenous RNA (ceRNA) network analyses, followed by in vitro assessment of both RNA and protein expression levels. Results: ceRNA network analysis revealed 7 candidate core molecules and 2 putative ceRNA axes—hsa_circ_0015475/hsa-miR-4753-3p/retinoic acid receptor-related orphan receptor alpha (RORA) and growth arrest-specific 5 (GAS5)/hsa-miR-10a-5p/RORA—which converge on the common messenger RNA RORA. In vitro assessment revealed that RORA messenger RNA and protein expression levels were reduced in osteosarcoma cell lines. A pan-cancer analysis further revealed that RORA was differentially expressed across multiple cancer types. Conclusion: This study revealed 2 potential RORA-related ceRNA axes, hsa_circ_0015475/hsa-miR-4753-3p/RORA and GAS5/hsa-miR-10a-5p/RORA, that may be associated with osteosarcoma-related molecular alterations. The reduced expression of RORA in osteosarcoma cell lines suggests its potential relevance to osteosarcoma biology.