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

• DOI: 10.1007/s00018-024-05146-x
• Publication Date: 2024-02-09T09:02:32Z
• Authors: Qiang Li; Yaju Wang; Xiangshu Meng; Wenjing Wang; Feifan Duan; Shuya Chen; Yukun Zhang; Zhiyong Sheng; Yu Gao; Lei Zhou
• Keywords: 0301 basic medicine; Methyltransferases; DNA Methylation; Lipid Metabolism; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Thyroid Cancer, Papillary; Cell Line, Tumor; Humans; Original Article; Thyroid Neoplasms; Stearoyl-CoA Desaturase; RNA Helicases; Cell Proliferation

AbstractPapillary thyroid carcinoma (PTC) stands as the leading cancer type among endocrine malignancies, and there exists a strong correlation between thyroid cancer and obesity. However, the clinical significance and molecular mechanism of lipid metabolism in the development of PTC remain unclear. In this study, it was demonstrated that the downregulation of METTL16 enhanced lipid metabolism and promoted the malignant progression of PTC. METTL16 was expressed at lower levels in PTC tissues because of DNMT1-mediated hypermethylation of its promoter. Loss- and gain-of-function studies clarified the effects of METTL16 on PTC progression. METTL16 overexpression increased the abundance of m6A in SCD1 cells, increasing RNA decay via the m6A reader YTHDC2. The SCD1 inhibitor A939572 inhibited growth and slowed down lipid metabolism in PTC cells. These results confirm the crucial role of METTL16 in restraining PTC progression through SCD1-activated lipid metabolism in cooperation with YTHDC2. This suggests that the combination of METTL16 and anti-SCD1 blockade might constitute an effective therapy for PTC.