The ACSL3–NNMT Axis Regulates Melanoma Cell Migration and Invasion In Vitro

Abnormal expression of long-chain acyl-CoA synthetase 3 (ACSL3) has been reported to be associated with the development and progression of various tumors. Thus, we investigated the precise effects and underlying mechanisms of ACSL3 on melanoma. ACSL3 affected melanoma cell migration and invasion in vitro. The downstream target nicotinamide N-methyltransferase (NNMT) was identified by RNA-seq and mass spectrometry. RT-qPCR and Western blot were performed for subsequent validation. ACSL3 activated the Interleukin 6/Signal Transducerand Activator of Transcription 3 (IL-6/STAT3) pathway and increased NNMT RNA stability, which promoted NNMT protein expression. NNMT overexpression promoted melanoma cell migration and invasion and reversed the inhibition of aggressive melanoma phenotypes caused by ACSL3 downregulation. The key metabolic phenotypes revealed that the ACSL3–NNMT axis modulates both glycolytic flux and fatty acid storage in melanoma cells. Overall, ACSL3 and NNMT are associated with melanoma cell migration and invasion in vitro and may represent candidate targets for further investigation.