Ldha Regulates Osteosarcoma Lung Metastasis through Hedgehog Signaling.

UNLABELLED: Osteosarcoma is the most common malignant bone tumor in children and adolescents, with a high propensity for lung metastasis, leading to poor prognosis. Lactate dehydrogenase A (LDHA), a key glycolytic enzyme, has been implicated in the progression and metastasis of various cancers. In this study, we demonstrated that Ldha knockdown reduced cell migration and invasion in murine osteosarcoma cells and decreased lung metastasis. RNA sequencing analysis revealed that Ldha knockdown was associated with the downregulation of Hedgehog signaling. Consistently, pharmacologic inhibition of Hedgehog signaling using vismodegib suppressed cell migration, invasion, and lung metastases in murine osteosarcoma cells. In human osteosarcoma cells, LDHA silencing downregulated Hedgehog signaling, and inhibition of Hedgehog signaling suppressed cell migration and invasion. These findings highlight the involvement of the Ldha-Hedgehog signaling axis in osteosarcoma lung metastases, providing insights into its molecular mechanisms and potential therapeutic targets.

SIGNIFICANCE: Ldha knockdown downregulates Hedgehog signaling and inhibits osteosarcoma lung metastasis, presenting a potential therapeutic target for osteosarcoma.