In conclusion, this study showed that continuous, dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than the parental cells, characterized by reduced migratory and invasive abilities, reduced expression of EMT markers and reduced expression of EHMT2, PRMT5, and SETD7/9 together with changes in their protein methylation profile. This evidence concerns the gene PRMT5 and cancer.