PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

The PPAR coactivator-1 alpha (PGC1 alpha) is an important transcriptional co-activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1 alpha is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1 alpha could sensitize NPC cells to radiotherapy. Mechanically, PGC1 alpha binds to CCAAT/enhancer binding protein beta (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1 alpha/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1 alpha could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1 alpha might improve the therapeutic efficacy of radiotherapy.