METTL3 and esophageal squamous cell carcinoma: Furthermore, in ESCC cells with METTL3 silencing, the overexpression of wild-type METTL3 (M3-WT), but not the enzyme-inactivated mutant METTL3 (M3-MUT, amino acids [aa]395-398, DPPW-APPA26), restored the m6A levels in the TNFR1 transcript (Figure 2E), suggesting that m6A modification of the TNFR1 transcript is dependent on the methyltransferase activity of METTL3.