We found that AGO2 transcript is positively correlated with MLL4 expression in the vast majority of human TCGA cancer types and CCLE cancer cell lines and loss of MLL4 decreases the expression of AGO2 in murine B16 cells and a few human cancer lines, indicating a direct and general role that MLL4 plays in transcriptional suppression of AGO2 expression in cancer cells irrespective of their tissue origin. Here, KMT2D is linked to cancer.