A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level.

A potential proliferative gene, NUDT6, is down-regulated by green tea catechins at the posttranscriptional level.
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DOI:
10.1016/j.jnutbio.2008.11.002
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发表时间:
2010-02
期刊:
The Journal of nutritional biochemistry
影响因子:
--
通讯作者:
Baek SJ
Baek SJ
中科院分区:
其他
文献类型:
--
作者:
Sukhthankar M;Choi CK;English A;Kim JS;Baek SJ

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本研究的主要目的是阐明绿茶儿茶素对NUDT6的抑制作用,并表征NUDT6的生物活性。我们的微阵列数据显示,绿茶成分表儿茶素没食子酸酯(ECG)抑制NUDT6的表达,并通过RT-PCR证实了这一点。随后,不同儿茶素的使用表明,表没食子儿茶素没食子酸酯(EGCG)的作用强于其他儿茶素。在转录后水平上,EGCG降低了NUDT6的RNA稳定性,表明其可能是NUDT6抑制的一种潜在机制。进一步克隆人NUDT6 mRNA的3'UTR导致EGCG处理导致荧光素酶活性降低。这种作用至少部分是由ERK和p38MAPK途径介导的。最后,过表达NUDT6的细胞在软琼脂中增殖和生长增加。这些发现为绿茶儿茶素抑制人类结直肠癌增殖基因NUDT6提供了一种新的机制。
The main aims of this study were to elucidate the effect of green tea catechins on NUDT6 suppression and to characterize NUDT6 biological activity. Our microarray data showed that the green tea component epicatechin gallate (ECG) suppressed NUDT6 expression, and this was confirmed by RT-PCR. Subsequently, the use of different catechins showed that the effect of epigallocatechin gallate (EGCG) was stronger than that of other catechins. At the post-transcriptional level, EGCG decreased the RNA stability of NUDT6, indicating it as a potential mechanism of NUDT6 suppression. Further cloning of 3’UTR of human NUDT6 mRNA resulted in a reduced luciferase activity by EGCG treatment. This effect was at least in part mediated by ERK and p38MAPK pathways. Finally, increased cell proliferation and cell growth in soft agar were observed in NUDT6 overexpressing cells. These findings provide a novel mechanism for suppression of the proliferative gene NUDT6 by green tea catechins in human colorectal cancer.
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