Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a metabolic enzyme that regulates the folate cycle from format production (Agarwal et al., 2019),It is a downstream target of MLT, which was found by Cui et al. to inhibit the development of HNSCC by inhibiting the expression of MTHFD1L mainly through downregulation of CREB1 phosphorylation,In a head and neck squamous cell carcinoma xenograft model, melatonin inhibited tumor growth by more than 60% (Cui et al., 2021). This evidence concerns the gene CREB1 and head and neck squamous cell carcinoma.