In this present study, consistent with current knowledge that the epigenetic modulation of genes is a critical mechanism underlying the CRC oncogenicity and disease progression, as well as the development of resistance to chemotherapeutics, we demonstrate a novel and previously undocumented epigenetic-based mechanism of 4-AAQB therapeutic activity in CRC, involving the down-regulation of tumor-promoting SOD2 by the suppressor ncRNA, hsa-miR-324-5p. Here, SOD2 is linked to colorectal carcinoma.