Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells
Open Access
- 27 March 2012
- journal article
- Published by Springer Science and Business Media LLC in Journal of Experimental & Clinical Cancer Research
- Vol. 31 (1), 27-9
- https://doi.org/10.1186/1756-9966-31-27
Abstract
Background Pure curcumin has been reported to down-regulate the expression of WT1 in leukemic cells. However, the molecular mechanism underlying the down-regulation of WT1 by curcumin is not completely delineated. The purpose of this present study is to identify a new miRNA-mediated mechanism which plays an important role in the anti-proliferation effects of curcumin in leukemic cells. Methods K562 and HL-60 cells were treated with different concentrations of curcumin for 24 and 48 hours, the level of miR-15a/16-1 and WT1 were detected by qRT-PCR and Western blotting. WT1 expression and cell proliferation were detected by Western blotting and CCK-8, after curcumin treated-K562 and HL-60 cells were transfected with anti-miR-15a/16-1 oligonucleotides. Results We found that pure curcumin upregulated the expression of miR-15a/16-1 and downregulated the expression of WT1 in leukemic cells and primary acute myeloid leukemia (AML) cells. Overexpression of miR-15a/16-1 deduced the protein level of WT1 in leukemic cells, but downregulation of WT1 by siRNA-WT1 could not increase the expression of miR-15a/16-1 in leukemic cells. These results reveal that curcumin induced-upregulation of miR-15a/16-1 is an early event upstream to downregulation of WT1. Furthermore, anti-miR-15a/16-1 oligonucleotides (AMO) partly reversed the downregulation of WT1 induced by pure curcumin in leukemic cells and AMO promoted the growth of curcumin treated-K562 and HL-60 cells. Conclusion Thus, these data suggest for the first time that pure curcumin downregulated the expression of WT1 partly by upregulating the expression of miR-15a/16-1 in leukemic cells. miR-15a/16-1 mediated WT1 downregulation plays an important role in the anti-proliferation effect of curcumin in leukemic cells.Keywords
This publication has 31 references indexed in Scilit:
- miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein levelJournal of Experimental & Clinical Cancer Research, 2011
- Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathwayBiochemical and Biophysical Research Communications, 2010
- Two new miR‐16 targets: caprin‐1 and HMGA1, proteins implicated in cell proliferationBiology of the Cell, 2009
- Up-regulation of miR-200 and let-7 by Natural Agents Leads to the Reversal of Epithelial-to-Mesenchymal Transition in Gemcitabine-Resistant Pancreatic Cancer CellsCancer Research, 2009
- Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studiesBioorganic & Medicinal Chemistry, 2009
- Wilms’ tumour gene 1 (WT1) as a target in curcumin treatment of pancreatic cancer cellsEuropean Journal of Cancer, 2009
- Evidence for dietary regulation of microRNA expression in cancer cellsNutrition Reviews, 2008
- MiR-15a and miR-16-1 cluster functions in human leukemiaProceedings of the National Academy of Sciences of the United States of America, 2008
- Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin geneBlood, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001