p73-Governed miRNA Networks: Translating Bioinformatics Approaches to Therapeutic Solutions for Cancer Metastasis.
p73-Governed miRNA Networks: Translating Bioinformatics Approaches to Therapeutic Solutions for Cancer Metastasis.
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DOI：
10.1007/978-1-4939-8982-9_2
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发表时间：
2019
影响因子：
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通讯作者：
Stella Logotheti;Stephan Marquardt;B. Pützer
中科院分区：
文献类型：
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作者：
Stella Logotheti;Stephan Marquardt;B. Pützer
转录因子p73合成了大量的异构体，与p53具有高度的结构和功能同源性，p53是一种著名的肿瘤抑制因子，也是著名的抗癌靶向“圣杯”。p73引起越来越多的关注，主要是因为：（a）与p53不同，p73在癌症中很少突变;（B）一些p73异构体可以抑制癌症的所有标志，和（c）它具有模拟p53，甚至p53突变细胞的肿瘤抑制功能的能力。这些属性使得p73及其下游通路对于治疗靶向具有吸引力，特别是在突变型p53驱动的癌症中。p73的功能至少部分地由微小RNA（miRNAs）介导，其构成p73支配的网络的节点组件。p73不仅调节关键miRNA基因的转录，而且还被预测通过与miRNA加工机制的组分形成蛋白质-蛋白质相互作用以不依赖于转录的方式影响miRNA群体。p73在miRNA转录和成熟中的这种组合作用似乎是亚型依赖性的，并且可以导致细胞miRNomes向抗癌或致癌结果的系统性转换。在这篇综述中，我们将联合收割机文献检索与生物信息学方法相结合，重建p73调控的miRNA网络，并讨论如何利用这些串扰开发下一代治疗方法。
The transcription factor p73 synthesizes a large number of isoforms and presents high structural and functional homology with p53, a well-known tumor suppressor and a famous “Holy Grail” of anticancer targeting.p73has attracted increasing attention mainly because (a) unlikep53,p73is rarely mutated in cancer, (b) some p73 isoforms can inhibit all hallmarks of cancer, and (c) it has the ability to mimic oncosuppressive functions of p53, even inp53-mutated cells. These attributes render p73 and its downstream pathways appealing for therapeutic targeting, especially in mutantp53-driven cancers. p73 functions are, at least partly, mediated by microRNAs (miRNAs), which constitute nodal components of p73-governed networks. p73 not only regulates transcription of crucial miRNA genes, but is also predicted to affect miRNA populations in a transcription-independent manner by developing protein-protein interactions with components of the miRNA processing machinery. This combined effect of p73, both in miRNA transcription and maturation, appears to be isoform-dependent and can result in a systemic switch of cell miRNomes toward either an anti-oncogenic or oncogenic outcome. In this review, we combine literature search with bioinformatics approaches to reconstruct the p73-governed miRNA network and discuss how these crosstalks may be exploited to develop next-generation therapeutics.