Identification of key targets and exploration of therapeutic molecular mechanisms of natural compound tangeretin in osteosarcoma.

Introduction: Osteosarcoma (OS) is an invasive and lethal malignancy showing a low 5 year survival rate, underscoring the need for identifying new therapeutic targets and their inhibitors to enhance prevention and treatment strategies.

Methods: In this study, in vitro experiments including CCK-8 assay, anchorage-independent growth assays, and plate cloning assays were used to detect the anti-proliferation ability of natural compound tangeretin towards OS cells. An integrated approach was performed including WGCNA and network pharmacology to identify the key genes of tangeretin for the treatment of OS. Multigene diagnostic model, reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis along with molecular docking analysis were further conducted to validate the reliability of the targets obtained by bioinformatics methods. Single-cell and gene enrichment analyses were chosen to explore the mechanism of tangeretin in OS.

Results: Hub genes identified by the bioinformatics strategy included ABCC1, AKR1C3, BACE1, and CA12. RT-qPCR validation and molecular docking analysis confirmed that ABCC1 and BACE1 were the most likely potential targets. A multigene diagnostic model for OS demonstrated moderate accuracy of the hub genes. Single-cell sequencing results indicated that these two hub targets were closely related to OS and provided more potential mechanisms for targeting OS.

Conclusion: Our research highlights the therapeutic potential of the natural compound tangeretin and its antineoplastic mechanisms in OS. It offers new insights into the molecular mechanisms of tangeretin, paving the way for the development of effective OS treatments.