By comparing DU145 and PC3 prostate cancer models bearing the mPGES-1 functional enzyme (transfected with scrambled control shRNA or CRISPR/Cas9 control, i.e. mPGES-1+/+ cells) with those in which the enzyme is silenced or deleted (knocked down or knocked out, i.e. mPGES-1−/− cells), we provide evidence that tumor-derived PGE-2 represses miRNA biogenesis, inhibiting Dicer expression by an autocrine mechanism. This evidence concerns the gene PTGES and Familial prostate cancer.