**2.5 3,3**′**-Diindolylmethane**

3,3′-diindolylmethane (DIM) is a naturally active compound found in stomach, which derived from indole-3-carbinol (I3C) that present in cruciferous vegetables. DIM has been reported to regulate several miRNAs expression in cancer. Tumor suppressor miRNAs was upregulated by DIM in prostate cancer cells including let-7, miR-34a and miR-150-5p by targeting EZH2, Notch1 and AR and Ahr, respectively [46].

DIM also upregulated tumor suppressor miR-200, which led to inhibit the expression of FoxM1 in breast cancer cells [47]. miR-212/132 cluster and miR-21 were upregulated by DIM, which downregulated the expression of Sox4 and Cdc25A, respectively in breast cancer [48, 49]. Moreover, DIM upregulated let-7b, let-7c, let-7d, let-7e, and miR-200b/c expression, which led to inhibit the expression of ZEB-1, E-cadherin in pancreatic cancer cells [50]. It has been reported miR-146a was upregulated upon treated with DIM and suppressed the expression of MTA2, NF-κB, IRAK1, EGFR in pancreatic cancer cells [51].

DIM showed the modulation of miRNAs expression in other inflammatory diseases. The expression of miR-106a, miR-20b, and miR-125b-5p were increased after treatment with DIM and suppressed the expression of IRAK4 and TNF-α to limit responses to TLRs activated by LPS in acute liver failure (ALF) animal model [52]. DIM significantly upregulated miR-200c, miR-146a, miR-16, miR-93, and miR-22 in brain CD4+ T cells and inhibited the expression of cyclin E1 and B-cell lymphoma-2 in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis [53].
