CD95 is part of a let-7/p53/miR-34 regulatory network.
CD95 is part of a let-7/p53/miR-34 regulatory network.
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CD95是Let-7/p53/miR-34监管网络的一部分。
DOI：
10.1371/journal.pone.0049636
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Peter ME
中科院分区：
文献类型：
--
作者：
Hau A;Ceppi P;Peter ME
死亡受体CD95（APO-1/Fas）在与其同源配体CD95L连接后介导凋亡诱导。已经鉴定了两种类型的CD95信号传导途径，其特征在于线粒体参与的不存在（I型）或存在（II型）。微RNA是一种非编码小RNA，负调控基因表达。它们是分化过程的重要调节剂，并且在许多人类癌症中经常被发现失调。我们最近发现，I型细胞表达较少的分化标记物let-7，因此可能代表比let-7高表达的II型细胞更晚期的肿瘤细胞。我们现在已经确定miR-34a作为对CD95介导的凋亡敏感的细胞的选择性标记。CD95和miR-34a都是p53靶基因，因此，癌细胞对CD95介导的凋亡的敏感性和对p53介导的DNA遗传毒性应激的响应能力都是相关的。有趣的是，虽然发现miR-34a与细胞响应遗传毒性应激的能力呈正相关，但let-7呈负相关。CD95的表达水平与let-7的表达呈负相关，表明CD 95调节let-7的表达。为了测试p53和miR-34a之间的联系，我们改变了CD95的表达。这影响了细胞激活p53和调节miR-34a的能力。我们的数据指向一个新的调控网络，包括p53，CD95，let-7和miR-34a，影响癌细胞的存活，分化和对凋亡信号的敏感性。这种调节网络的癌症干细胞的可能相关性进行了讨论。
The death receptor CD95 (APO-1/Fas) mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I) or presence (Type II) of mitochondrial involvement. Micro(mi)RNAs are small noncoding RNAs that negatively regulate gene expression. They are important regulators of differentiation processes and are found frequently deregulated in many human cancers. We recently showed that Type I cells express less of the differentiation marker miRNA let-7 and, hence, likely represent more advanced tumor cells than the let-7 high expressing Type II cells. We have now identified miR-34a as a selective marker for cells that are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of cancer cells to CD95-mediated apoptosis and the ability to respond to p53 mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found to positively correlate with the ability of cells to respond to genotoxic stress, let-7 was negatively correlated. The expression level of CD95 inversely correlated with the expression of let-7 suggesting regulation of let-7 expression by CD95. To test a link between p53 and miR-34a, we altered the expression of CD95. This affected the ability of cells to activate p53 and to regulate miR-34a. Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possible relevance of this regulatory network for cancer stem cells is discussed.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
DOI：
10.1016/j.bbrc.2011.04.074
发表时间：
2011-05-13
影响因子：
3.1
作者：
Geng, Li;Zhu, Bin;Yang, Jia-Mei
通讯作者：
Yang, Jia-Mei
影响因子：
20.3
作者：
Del-Rey, Manuel;Ruiz-Contreras, Jesus;Allende, Luis M.
通讯作者：
Allende, Luis M.