AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism
Year: 2025
Type: article
Abstract: Background: Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors, however, its function in osteosarcoma is unclear. This study aimed to explore the role of glycerolipid metabolism in osteosarcoma. Methods: We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and single-cell RNA sequencing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma. Tumor-associated macrophages (TAMs) and their interactions with immune cells were examined through single-cell analysis and co-culture experiments. Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6 (LPAR6) inhibitors. Results: in osteosarcoma cells resulted in elevated lysophosphatidic acid (LPA) levels, which regulated the immune environment, inhibiting cytotoxic T cell function through TAMs' LPAR6 signaling. LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion, including interleukin-6 (IL-6) and interleukin-10 (IL-10). Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6. Conclusion: is an important gene related to the prognosis of osteosarcoma. Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment, particularly in immunotherapy contexts.
Authors: Shenghui Su, Yu Zeng, Jiaxin Chen, Xieping Dong
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7082969821