In terms of acetylation, metformin inhibits SMAD3 phosphorylation and hinders the KAT5-SMAD3 interaction, which reduces KAT5-mediated K333 acetylation of SMAD3 to inhibit SMAD3 transcription and TRIB3 expression, thereby restoring autophagy and combating melanoma progression [94]. Here, SMAD3 is linked to melanoma.