Mechanistically, METTL16 enhanced m6A modification of MSMO1, stabilizing its transcript via IGF2BP2 and disrupting intracellular cholesterol homeostasis, which triggered ER stress and activated MAPK-p38/ NF-κB signaling by promoting TAK1/TAB complex formation and TAK1 autophosphorylation, thereby driving CRC progression. This evidence concerns the gene NFKB1 and colorectal carcinoma.