To evaluate whether nonmethylated peptides containing methylation sites could inhibit endogenous SMAD3 methylation and further restrain cancer metastasis, we first synthesized peptides that contained SMAD3 methylation sites (48–58 aa for peptide 1 and 328–338 aa for peptide 2) with a trans-activator of transcription (TAT) tag placed in its N-terminal region (with a TAT domain as a negative control) (Figure 6A). The gene discussed is SMAD3; the disease is cancer.