摘要
背景:放射疗法是普通和晚期肺癌患者最广泛使用的治疗方法。此外,放射治疗引起的临床毒性分为急性放射性肺炎和晚期肺纤维化。上皮 - 间质转化(EMT)是一个复杂的生理过程,涉及许多信号分子和蛋白质,如衔接蛋白和转录因子。它被确定为纤维化,伤口愈合和癌症的重要机制。辐射诱导的肺部EMT中出现了多种生物标志物,其中一些是获得性的(N-钙粘蛋白,波形蛋白和纤维连接蛋白等),其中一些在上皮细胞转变过程中被抑制(E-钙粘蛋白,zona occludens- 1)。 目的:在目前的综述中,我们强调了辐射诱导的肺EMT信号通路及其介质。我们还讨论了癌症,纤维化及其表观的EMT。 结果:辐射诱导的肺EMT受MAPK,NF-κB,Wnt,microRNA和组蛋白修饰等多种信号通路控制。转录因子如Snail,slug,twist,ZEB1(Zinc finger E-box binding-1)和ZEB2(Zinc finger E-box binding-2)蛋白是连接辐射诱导的EMT和纤维化的诱导物。表观遗传调节是基因组结构和功能的可遗传变化,其发生时序列没有任何变化。几种方法显示了表观遗传修饰及其抑制剂在控制纤维化和癌症中的作用。只有有限的报告集中于了解辐射诱导的肺部EMT的表观遗传调节。 结论:目前的综述重点关注辐射诱导的肺纤维化和EMT的最新发现,从而提供了重要信号通路的一些信息,其随后表达的基因和参与EMT的蛋白质。该综述还讨论了可用于治疗EMT相关疾病,即纤维化,癌症的各种抑制剂。
关键词: 辐射,EMT,表观遗传学,抑制剂,纤维化,信号通路。
图形摘要
Current Drug Targets
Title:Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators
Volume: 19 Issue: 10
关键词: 辐射,EMT,表观遗传学,抑制剂,纤维化,信号通路。
摘要: Background: Radiotherapy is the most widely used treatment method for average and advanced lung cancer patients. Moreover, the clinical toxicities caused by radiotherapy are categorized into acute radiation pneumonitis and late pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a complex physiological process involves many signaling molecules and proteins like adaptor proteins, and transcriptional factors. It was identified as a significant mechanism for fibrosis, wound healing and also cancer. A variety of biomarkers have appeared in radiation-induced lung EMT, some of which are acquired (N-cadherin, vimentin and fibronectin, etc.) and some of which are repressed during the transition of epithelial cells (E-cadherin, zona occludens-1).
Objective: In the current review, we highlighted the radiation-induced lung EMT signaling pathway and their mediators. We also discuss the EMT in cancer, fibrosis and its epigentics.
Results: Radiation-induced lung EMT is controlled by numerous signaling pathways like MAPK, NF- κB, Wnt, microRNAs and histone modifications. Transcriptional factors such as Snail, slug, twist, ZEB1 (Zinc finger E-box binding-1) and ZEB2 (Zinc finger E-box binding-2) proteins are inducers linking radiation-induced EMT and fibrosis. Epigenetic modulations are heritable changes in the structure and function of the genome that occurs without any change in the sequence. Several approaches showed the role of epigenetic modifications and its inhibitors in controlling fibrosis and cancer. Only limited reports are focused on understanding the epigenetic regulations of radiation-induced lung EMT.
Conclusion: The current review focused on recent findings regarding radiation-induced lung fibrosis and EMT, thus provides some information on important signaling pathways, its subsequent expression of genes and proteins involved in EMT. This review also discussed various inhibitors that could be used to treat EMT related diseases, i.e., fibrosis, cancer.
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Cite this article as:
Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators, Current Drug Targets 2018; 19 (10) . https://dx.doi.org/10.2174/1389450119666180207092234
DOI https://dx.doi.org/10.2174/1389450119666180207092234 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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