METTL16 Promotes Head and Neck Squamous Cell Carcinoma Progression via m6A ‐Mediated Stabilization of SREBP2 mRNA and Enhanced Cholesterol Biosynthesis

N6-methyladenosine (m6A) modification is a crucial epigenetic event in the development of head and neck squamous cell carcinoma (HNSCC). Here, we show that methyltransferase-like 16 (METTL16) expression is elevated in the tumor tissues of patients with HNSCC and is associated with poor prognosis. In addition, our data show that METTL16 promotes the proliferation of HNSCC cells in vitro and in vivo by enhancing cholesterol biosynthesis. Mechanistically, METTL16 catalyzes a key transcription factor in cholesterol biosynthesis-sterol regulatory element-binding transcription factor 2 (SREBP2) m6A modification and then stabilizes SREBP2 mRNA and ultimately elevates SREBP2 mRNA expression in HNSCC cells. Moreover, we validate that METTL16 promotes HNSCC progression dependent on SREBP2 mRNA expression. Overall, our results reveal a novel function of METTL16 in regulating SREBP2 expression, revealing a previously unrecognized METTL16/SREBP2 pathway in HNSCC cells.