miR-138转录可下调p33ING1在衰老细胞中的表达

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中国生物化学与分子生物学报 ›› 2009, Vol. 25 ›› Issue (10) : 938-942.

研究论文

miR-138转录可下调p33ING1在衰老细胞中的表达

邹平¹⁾,段承刚²⁾,何涛²⁾

作者信息 +

miR-138 Downregulates p33ING1 Expression at Post-transcriptional Level in Senescent Cells

ZOU Ping¹⁾, DUAN Cheng-Gang²⁾, HE Tao^2)*

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文章历史 +

摘要

p33ING1参与了多种生物学过程，包括细胞生长抑制、凋亡、DNA损伤修复、染色质重塑等．近来研究显示,p33在细胞衰老过程中表达降低，这可能与衰老细胞的抗凋亡有关．但p33在衰老细胞中表达下调的分子机理仍不清楚．我们发现，在衰老细胞中miR-138表达升高与p33基因的表达降低密切相关．以下实验结果支持如此结论：(1)与年轻细胞相比，带p33ING1 3′UTR 报告载体荧光素酶活性在衰老细胞中降低；突变3′UTR上的miR-138结合位点可升高报告载体荧光素酶在衰老细胞中的活性；(2)在衰老细胞中miR-138的表达升高；(3)在年轻细胞中,过表达miR-138不仅可抑制带p33ING1 3′UTR 报告载体荧光素酶活性，而且下调细胞内p33ING1基因mRNA和蛋白水平.与此相反，抑制miR-138活性可升高带p33ING1 3′UTR 报告载体荧光素酶活性，并且上调细胞内p33ING1基因mRNA和蛋白水平．这些结果表明,p33ING1基因是miR-138的靶基因；在衰老过程中，miR-138表达升高, 由此导致该基因的表达降低．

Abstract

Studies have showed that p33 is involved in growth inhibition, apoptosis, chromatin remodeling, DNA repair and tumor suppression. Recent report demonstrated that p33 expression decreases in senescent cells compared to young cells, which likely contributes to the resistance of senescent cells to apoptotic induction. In this report, we show that miR-138 contributes to the decrease of p33 expression in senescent cells. This conclusion is supported by below observations: (1) Luciferase activity from the reporter vector with 3′UTR in senescent cells is lower compared to it in young cells, and mutation of miR-138 binding site resulted in the increase of luciferase activity in senescent cells; (2) miR-138 expression increased in senescent cells; (3) miR-138 overexpression in young cells down-regulated endogenous p33ING1 expression at mRNA and protein levels. In contrast, its knockdown increased endogenous p33ING1 expression. These results indicate that the up-regulation of miR-138 expression contributes to the decrease of p33ING1 expression during senescent process.

导出引用

邹平,段承刚,何涛. miR-138转录可下调p33ING1在衰老细胞中的表达[J]. 中国生物化学与分子生物学报, 2009, 25(10): 938-942

ZOUPing;DUANCheng-Gang;HETao.

miR-138 Downregulates p33ING1 Expression at Post-transcriptional Level in Senescent Cells

[J]. Chinese Journal of Biochemistry and Molecular Biology, 2009, 25(10): 938-942

参考文献

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收稿日期	修回日期	出版日期
2009-04-13	2009-05-29	2009-10-20
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2009-10-20

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