Tumor progression requires a lot of energy. Energy-rich lipids are good energy fuel for tumor growth. In our OSCC tissue array, we identified several upregulated genes associated with FAO, including CPT1A. CPT1A is the rate-limiting enzyme in fatty acid metabolism. Blocking FAO by knockdown of CPT1A or etomoxir treatment could effectively inhibit the proliferation, invasion and migration of OSCCs, suggesting that CPT1A-mediated FAO plays an important role in oral carcinogenesis. Besides, overexpressed CPT1A promoted LDs degradation by lipolysis and lipophagy, and then releasing more free fatty acids for mitochondrial FAO to generate ATP. In contrast, knockdown of CPT1A resulted in the accumulation of LDs. We further found that CPT1A is a functional target of miR-378a-5p. MiR-378a-5p was not only significantly reduced in tumors but also strongly negatively correlated with CPT1A expression. Overexpressed miR-378a-5p can accumulate LDs and significantly inhibit the proliferation, invasion and migration of OSCC by inhibiting CPT1A. These results suggest that miR-378a-5p/CPT1A-mediated abnormal mitochondrial fatty acid metabolism may play an important role in oral cancer development.
