The results demonstrated that KSHV infection stimulated the secretion of HMGB1 in human endothelial cells, and that HMGB1 plays a critical role in KS pathogenesis by promoting cytokine and growth factor secretion and facilitating cellular sphere maintenance, suggesting that targeting HMGB1 could be a potential therapeutic strategy for treating KS. The gene discussed is HMGB1; the disease is Kaposi's sarcoma.