Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
Clin Genet. 2020 Oct;98(4):322-330. doi: 10.1111/cge.13750. Epub 2020 Apr 20.
The neuropeptide substance P (SP) triggers a variety of tumor-promoting signaling pathways through the activation of neurokinin-1receptor (NK1R), a class of neurokinin G protein-coupled receptors superfamily. Recent researches in our and other laboratories have shown the overexpression of both SP and NK1R in breast cancer (BC) patients. SP/NK1R signaling is strongly implicated in the pathogenesis of BC through affecting cell proliferation, migration, metastasis, angiogenesis, and resistance. Therefore, SP/NK1R signaling responses must be rigorously regulated; otherwise, they would contribute to a more aggressive BC phenotype. Recently, microRNAs (miRNAs) as a specific class of epigenetic regulators have been shown to regulate NK1R and thus, controlling SP/NK1R signaling responses in BC. This review summarizes the current knowledge of the role of SP/NK1R signaling and its therapeutic potentials in BC. We also provide an overview regarding the effects of miRNA-mediated NK1R regulatory mechanisms in controlling BC tumorigenesis to gain a clearer view and thus better management of cancer.
神经肽 P 物质（SP）通过激活神经激肽-1 受体（NK1R）触发多种促进肿瘤的信号通路，NK1R 是神经激肽 G 蛋白偶联受体超家族的一类。我们和其他实验室的最近研究表明，在乳腺癌（BC）患者中 SP 和 NK1R 的表达均过度。SP/NK1R 信号通过影响细胞增殖、迁移、转移、血管生成和耐药性，强烈参与 BC 的发病机制。因此，SP/NK1R 信号反应必须受到严格调控；否则，它们将导致更具侵袭性的 BC 表型。最近，作为一类特定的表观遗传调控因子的 microRNAs（miRNAs）已被证明可以调节 NK1R，从而控制 BC 中的 SP/NK1R 信号反应。这篇综述总结了 SP/NK1R 信号在 BC 中的作用及其治疗潜力的最新知识。我们还概述了 miRNA 介导的 NK1R 调节机制在控制 BC 肿瘤发生中的作用，以更清楚地了解和更好地管理癌症。
