Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells

Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells
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DOI:
10.1016/j.jnutbio.2008.12.003
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发表时间:
2010-02-01
影响因子:
5.6
通讯作者:
Kwok, Tim Tak
Kwok, Tim Tak
中科院分区:
医学2区
文献类型:
--
作者:
Tsang, Wing Pui;Kwok, Tim Tak

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表没食子儿茶素没食子酸酯(EGCG)是一种主要类型的绿茶多酚,已知具有预防癌症的作用。MicroRNAs (miRNAs)由19到25个核苷酸组成,被认为在基因调控中很重要。在本研究中,我们研究了EGCG对人类癌细胞中miRNAs表达的影响,这方面尚未有报道。通过miRNA芯片分析,发现EGCG处理可改变人肝癌HepG2细胞中部分miRNA的表达,其中上调13个,下调48个。miR-16是EGCG上调的mirna之一,其靶基因之一被证实为抗凋亡蛋白Bcl-2。EGCG诱导HepG2细胞凋亡,下调Bcl-2表达。转染anti-miR-16 inhibitor可抑制miR-16的表达,抵消EGCG对Bcl-2下调和细胞凋亡的影响。本研究结果证实了miR-16在介导EGCG细胞凋亡中的作用,也支持了mirna在调控EGCG生物活性中的重要性。(C) 2010爱思唯尔公司版权所有。
Epigallocatechin gallate (EGCG) is a major type of green tea polyphenols and is known to have cancer prevention effect. MicroRNAs (miRNAs) are 19 to 25 nucleotides and are believed to be important in gene regulation. In the present study, the influence of EGCG on the expressions of miRNAs in human cancer cells was investigated as this has not yet been reported. By miRNA microarray analysis, EGCG treatment was found to modify the expressions of some of the miRNAs in human hepatocellular carcinoma HepG2 cells, 13 were up-regulated and 48 were down-regulated. miR-16 is one of the miRNAs up-regulated by EGCG and one of its target genes is confirmed to be the anti-apoptotic protein Bcl-2. EGCG treatment induced apoptosis and down-regulated Bcl-2 in HepG2 cells. Transfection with anti-miR-16 inhibitor suppressed miR-16 expression and counteracted the EGCG effects on Bcl-2 down-regulation and also induction of apoptosis in cells. Results from the present study confirm the role of miR-16 in mediating the apoptotic effect of EGCG and also support the importance of miRNAs in the regulation of the biological activity of EGCG. (C) 2010 Elsevier Inc. All rights reserved.