The sodium/iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates active iodide transport into the thyroid gland and into several extrathyroidal tissues. NIS-mediated iodide uptake plays a pivotal role in the biosynthesis of thyroid hormones, of which iodide is an essential constituent. For 80 years, radioiodide has been used for the diagnosis and treatment of thyroid cancer, a successful theranostic agent that is extending its use to extrathyroidal malignancies. The purpose of this review is to focus on the most recent findings regarding the mechanisms that regulate NIS both in thyroid and extra-thyroidal tissues. Among other issues, we discuss the different transcriptional regulatory elements that govern NIS transcription in different tissues, the epigenetic modifications that regulate its expression, and the role that miRNAs play in fine-tuning NIS after being transcribed. A review on how hormones, cytokines, and iodide itself regulate NIS is provided. We also review the present stage of understanding NIS dysregulation in cancer, occupied mainly by convergent signaling pathways and by new insights in the route that NIS follows through different subcellular compartments to the plasma membrane. Furthermore, we cover NIS distribution and function in the increasing number of extrathyroidal tissues that express the symporter, as well as the role that NIS plays in tumor progression independently of its transport activity.

中文翻译：

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甲状腺和甲状腺外组织中 NIS 表达和活性的复杂调节。

钠/碘同向转运体 (NIS) 是一种内在的质膜蛋白，可介导活跃的碘转运到甲状腺和几个甲状腺外组织。NIS 介导的碘摄取在甲状腺激素的生物合成中起关键作用，其中碘是必不可少的成分。80 年来，放射性碘一直被用于甲状腺癌的诊断和治疗，这是一种成功的治疗诊断剂，正在将其应用扩展到甲状腺外恶性肿瘤。本综述的目的是关注关于在甲状腺和甲状腺外组织中调节 NIS 的机制的最新发现。除其他问题外，我们讨论了在不同组织中控制 NIS 转录的不同转录调控元件，调节其表达的表观遗传修饰，以及miRNA在转录后在微调NIS中所起的作用。提供了关于激素、细胞因子和碘化物本身如何调节 NIS 的综述。我们还回顾了理解癌症中 NIS 失调的现阶段，主要由收敛的信号通路和对 NIS 通过不同亚细胞区室到达质膜的途径的新见解占据。此外，我们涵盖了 NIS 在越来越多的表达同向转运蛋白的甲状腺外组织中的分布和功能，以及 NIS 在肿瘤进展中所起的独立于其转运活性的作用。主要由会聚信号通路和 NIS 通过不同亚细胞区室到达质膜的途径的新见解占据。此外，我们涵盖了 NIS 在越来越多的表达同向转运蛋白的甲状腺外组织中的分布和功能，以及 NIS 在肿瘤进展中所起的独立于其转运活性的作用。主要由会聚信号通路和 NIS 通过不同亚细胞区室到达质膜的途径的新见解占据。此外，我们涵盖了 NIS 在越来越多的表达同向转运蛋白的甲状腺外组织中的分布和功能，以及 NIS 在肿瘤进展中所起的独立于其转运活性的作用。