However, the decreased expression of Edn1 was probably caused by a different mechanism of action, which might have been activated by the increased levels of EdnrB and/or Ece1 mRNA, as suggested by the short but discernable time lag between the increased expression of EdnrB and/or Ece1 mRNA and the decreased expression of Edn1. To better understand this situation, we set up experiments in which human and rat CRC cells were treated with the demethylating agent DAC, which acts through inhibition of DNA methyltransferase enzymes DNMT1 and DNMT3 (Ning et al., 2016). This evidence concerns the gene EDN1 and colorectal carcinoma.