MiR-34, SIRT1 and p53 The feedback loop
MiR-34, SIRT1 and p53 The feedback loop
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DOI：
10.4161/cc.8.5.7753
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发表时间：
2009-03-01
期刊：
影响因子：
4.3
通讯作者：
Lowenstein, Charles J.
中科院分区：
文献类型：
--
作者：
Yamakuchi, Munekazu;Lowenstein, Charles J.
microRNA（miRNAs）是一类调控基因表达的非编码小RNA。一些研究已经将miRNA的失调与肿瘤发生联系起来。TP 53是人类癌症中最常见的突变基因之一，其基因产物p53激活一组miRNA的转录，包括miR-34家族的miRNA。miR-34家族调节细胞周期进程、细胞衰老和凋亡，但miR-34的靶点尚未完全确定。我们最近发现miR-34 a抑制SIRT 1，这是一种调节细胞衰老并限制寿命的基因。SIRT 1还通过去乙酰化和稳定p53来调节p53依赖性凋亡。我们还发现SIRT 1通过调节p53活性介导miR-34 a激活凋亡。基于这一观察，我们提出了一个正反馈环，其中p53诱导miR-34 a的表达，miR-34 a抑制SIRT 1，增加p53活性。
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Several studies have linked dysregulation of miRNA with tumorigenesis. The TP53 is one of the most commonly mutated genes in human cancers, and its gene product p53 activates transcription of a set of miRNA including the miR-34 family of miRNA. The miR-34 family regulates cell cycle progression, cellular senescence and apoptosis, but the targets of miR-34 are not completely defined. We recently found that miR-34a inhibits SIRT1, a gene that regulates cellular senescence and limits longevity. SIRT1 also regulates p53 dependent apoptosis through deacetylating and stabilizing p53. We also discovered that SIRT1 mediates miR-34a activation of apoptosis by regulating p53 activity. Based on this observation, we propose a positive feedback loop, in which p53 induces expression of miR-34a which suppresses SIRT1, increasing p53 activity.