Glienke and Bergmann showed that siRNA-reduced WT1 mRNA expression was associated with a decreased cell proliferation
in K562 and HL-60 cells after transfection for 24 and 48 h . Several studies indicated that pure Selleck Saracatinib curcumin downregulated the expression of WT1 in leukemic cell lines . Moreover, combined treatment with curcumin and siRNA targeting WT1 resulted in a significant inhibition of cell proliferation compared to curcumin-treated cells alone in pancreatic cancer cells. All these data suggest that WT1 plays an important role in the anti-proliferative effects of curcumin. However, the mechanism by which pure curcumin downregulates BIBF1120 WT1 expression is still unknown. Our data show for the first time that pure curcumin downregulates WT1 expression via miRNAs pathway. The gene expression is regulated via a complicated network. Semsri et al. reported that pure curcumin decreased the mRNA and protein levels
of WT1 through attenuating WT1 auto-regulatory function and inhibiting PKCalpha signaling in K562 cells . Our data showed that curcumin downregulated the expression of WT1 via miRNAs mediated pathway. However, whether other regulating factors are involved in the regulation is still not Selleck BLZ945 completely delineated. Therefore it is difficult to accurately calculated how much of the down-regulation of WT1 in the curcumin- treated cells is attributable to the action of the miRNAs. Our previous data had showed overexpression of miR-15a/16-1 downregulated the protein level of WT1 but not mRNA level . However, Interleukin-3 receptor in this report curcumin decreased the mRNA and protein levels of WT1 in leukemic
cells. Therefore, it is obvious that additional mechanisms  other than the induction of miR-15a/16-1 expression contribute to curcumin-induced WT1 downregulation. Taken together, as Additional file 1: Figure S2 indicated pure curcumin inhibited the cell growth partly through miR-15a/16-1 mediated downregulation of WT1. Each miRNA typically targets mRNAs of hundreds of distinct genes by pairing to the mRNAs of protein-coding genes. Previous data had reported that Bcl-2 , WT1 , caprin-1  and HMGA1  were the target genes by miR-15a/16-1. WT1 and Bcl-2 are highly expressed in leukemic cells and function as oncogenes. The use of SiRNAs against WT1 and Bcl-2 in leukemic cells could effectively inhibit leukemic cells growth . Overexpression of miR-15a/16-1 in leukemic cells suppressed cell growth probably through targeting WT1 and Bcl-2. However it is difficult to estimate how much of the inhibition of cell growth in leukemic cells is attributable to the downregulation of WT1 or Bcl-2. Recent studies have shown that natural agents, including curcumin, isoflavone, and EGCG, can regulate the expression of many miRNAs which increase the sensitivity of cancer cells to conventional agents and thereby suppress tumor cell proliferation [23, 24]. Zhang et al.