METTL16 inhibits papillary thyroid cancer tumorigenicity through m6A/YTHDC2/SCD1-regulated lipid metabolism

Papillary thyroid carcinoma (PTC) is the most common type of endocrine cancer, and there is a strong association between thyroid cancer and obesity. However, the clinical significance and molecular mechanisms of lipid metabolism in the development of PTC are not fully understood. This study demonstrated that downregulation of METTL16 enhances lipid metabolism and promotes the malignant progression of PTC. METTL16 levels were found to be lower in PTC tissues due to hypermethylation of its promoter mediated by DNMT1. Loss- and gain-of-function experiments revealed the impact of METTL16 on PTC progression. Overexpression of METTL16 increased m6A modification in SCD1 cells, leading to enhanced RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed lipid metabolism in PTC cells. These findings confirm the critical role of METTL16 in suppressing PTC progression through SCD1-mediated lipid metabolism in collaboration with YTHDC2. This suggests that targeting both METTL16 and SCD1 could represent a promising therapeutic strategy for PTC.