The E2F1-miRNA Cancer Progression Network
The E2F1-miRNA Cancer Progression Network
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DOI：
10.1007/978-94-007-5590-1_8
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Puetzer, Brigitte M.
中科院分区：
文献类型：
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作者：
Knoll, Susanne;Emmrich, Stephan;Puetzer, Brigitte M.
转录因子E2 F1具有双重性质，作为肿瘤抑制因子和癌基因。细胞应激如DNA损伤或促有丝分裂信号传导导致E2 F1的活化，E2 F1在保守的细胞抗肿瘤保护机制的背景下作为细胞凋亡的介体。然而，在高度侵袭性的化疗耐药肿瘤如恶性黑色素瘤和前列腺癌/膀胱癌中，它关闭了这种作用，并作为癌症进展的促进剂。E2 F1介导的侵袭性的可能原因是由重要肿瘤抑制基因的表观遗传失活引起的细胞死亡途径中的缺陷，这通常发生在晚期癌症中并导致化学抗性。然而，E2 Fs在侵袭和转移中的作用的确切机制在很大程度上是未知的。不同的报道暗示了E2 F1和microRNA（miRNAs或miRs）之间存在反馈环。miR被E2 F1激活，并且转录因子本身或E2 F1的生长调节功能所必需的细胞基因被不同的miRNA抑制。这种相互调节可能影响E2 F1促凋亡与促生存功能之间的平衡。在下文中，我们将总结一些miRNA-E2 F1-相互作用有助于一个复杂的调控网络。
The transcription factor E2F1 exhibits dual properties, acting as a tumor suppressor and oncogene. Cellular stress such as DNA damage or mitogenic signaling leads to the activation of E2F1 as a mediator of apoptosis in the context of a conserved cellular anti-tumorigenic safeguard mechanism. However in highly aggressive chemoresistant tumors like malignant melanoma and prostate/bladder cancer it switches off this role and acts as promoter of cancer progression. Possible reasons for E2F1 mediated aggressiveness are defects in cell death pathways caused by epigenetic inactivation of important tumor suppressor genes, which often occur in late stage cancer and contribute to chemoresistance. Nevertheless exact mechanisms underlying E2Fs role in invasiveness and metastasis are largely unknown. Different reports hint towards the existence of feedback loops between E2F1 and microRNAs (miRNAs or miRs). MiRs are activated by E2F1 and either the transcription factor itself or cellular genes necessary for the growth regulating function of E2F1 are inhibited by different miRNAs. This mutual regulation possibly influences the balance between E2F1s proapoptotic versus prosurvival function. In the following we will summarize some miRNA-E2F1-interactions contributing to a complex regulatory network.