Targeting the hsa_circ_0000253/miR-7/COL5A2 Axis: Unveiling CCT-018159's Role in Halting Osteosarcoma Progression

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, marked by aggressive local invasion and early metastasis. This study investigated the regulatory role of the hsa_circ_0000253/miR-7/COL5A2 axis and the therapeutic potential of CCT-018159 in OS progression. Differential expression and ceRNA network analyses identified hsa_circ_0000253 as a key regulator. Functional experiments demonstrated that silencing hsa_circ_0000253 or COL5A2 suppressed OS cell proliferation and migration, whereas inhibition of miR-7 enhanced these processes. Single-cell transcriptomics revealed distinct OS cell subclusters, with high-risk cells characterized by elevated expression of COL5A2, IGF1R, COL1A1, and COL1A2, indicating progression toward aggressive phenotypes. Molecular docking further identified CCT-018159 as a candidate drug capable of markedly reducing OS cell proliferation and migration. These findings highlight the hsa_circ_0000253/miR-7/COL5A2 axis as a critical driver of OS malignancy and suggest CCT-018159 as a promising therapeutic agent, warranting further in vivo validation and clinical exploration.