Fig. 6

Both genetic and chemical inhibition of HSF1 attenuate colorectal carcinogenesis driven by active Wnt signaling. a Expression of HSF1 protein in bowel tissue of APCmin/+ mice was analyzed by western blotting. b miR455-3p expression in bowel tissue of APCmin/+ mice was analyzed by RT-PCR. c and d The number of polyps per mouse in APCmin/+ and APCmin/+ mice when HSF1 was genetically knocked out or chemically inhibited mice was counted. e The downstream targets of HSF1 in APCmin/+ treated with KNK437 and APCmin/+HSF1+/− mice were analyzed by PT-PCR. Asterisks (*) indicate a P < 0.05. f Working model: When Wnt/β-catenin was inactivated, the transcription of COL27A1, the host gene of miR455-3p (miR455HG), was increased so that more miR455-3p was generated to occupy HSF1 mRNA 3′-UTR and prevent it from METTL3-mediated m6A modification, thus repressing HSF1 translation. In contrast, upon Wnt/β-catenin activation, miR455-3p generation was repressed so that HSF1 mRNA accessible for METTL3 binding and m6A modification. Eventually HSF1 translation was stimulated to promote colorectal carcinogenesis