In contrast to a previous report in which SIRT6 inhibited the Notch pathway by significantly reducing the level of H3K9ac in the promoter region of Notch1 and Notch4 in podocyte injury 54, we found that SIRT6 activated the Notch pathway in prostate cancer, indicating that a different molecular mechanism of the activation of Notch pathway by SIRT6 might exist in prostate cancer. This evidence concerns the gene NOTCH4 and prostate cancer.