Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells

被引：66

作者：

Gao, Shen-meng ^{[2
]}

Yang, Jun-jun ^{[3
]}

Chen, Chi-qi ^{[2
]}

Chen, Jun-jie ^{[2
]}

Ye, Li-ping ^{[2
]}

Wang, Lu-yao ^{[2
]}

Wu, Jian-bo ^{[2
]}

Xing, Chong-yun ^{[1
]}

Yu, Kang ^{[1
]}

机构：

[1] Wenzhou Med Coll, Affiliated Hosp 1, Dept Hematol, Wenzhou 325000, Peoples R China

[2] Wenzhou Med Coll, Affiliated Hosp 1, Lab Internal Med, Wenzhou 325000, Peoples R China

[3] Wenzhou Med Coll, Affiliated Hosp 2, Clin Lab, Wenzhou 325000, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2012年 / 31卷

基金：

中国国家自然科学基金;

关键词：

Curcumin; WT1; miR-15a; miR-16-1; MINIMAL RESIDUAL DISEASE; GENE-EXPRESSION; MICRORNAS; PROLIFERATION; SUPPRESSOR; TARGET; TOOL; PCR;

D O I：

10.1186/1756-9966-31-27

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页数：9

共 30 条

[1]

Curcumin inhibits WT1gene expression in human leukemic K562 cells [J].