RHBDL2 Drives Lipid Metabolic Reprogramming and Osteosarcoma Progression via USP3-Mediated Deubiquitination of PPT1
Osteosarcoma (OS), a highly malignant bone tumor, is characterized by rapid progression and poor prognosis, with lipid metabolic reprogramming playing a crucial role in its pathogenesis. This study investigates the role of RHBDL2 in OS progression and its therapeutic potential. We demonstrate that RHBDL2 is overexpressed in OS tumor tissues, correlating with poor prognosis. RHBDL2 suppression significantly inhibits OS cell proliferation, migration, and lipid metabolism while enhancing apoptosis. Mechanistically, RHBDL2 interacts with USP3, enhancing its expression to stabilize PPT1 by removing ubiquitin chains, thereby promoting lipid synthesis and storage. Importantly, we identified Epigallocatechin gallate (EGCG) as a small-molecule inhibitor that disrupts the RHBDL2/USP3 interaction, potentially offering a therapeutic strategy to inhibit osteosarcoma progression without affecting physiological bone remodeling.