放射性碘131（RAI）是分化型甲状腺癌（DTC）的选择治疗方法。约有5％至15％的DTC患者变得RAI难治，这是由于碘代谢组分，特别是Na / I共转运体（NIS）的表达/功能丧失所致。我们寻找与RAI难治性DTC相关的miRNA谱，以发现可能成为重分化治疗潜在靶点的新生物标志物。我们分析了26个DTC组织中754个miRNA的表达情况：其中12个对RAI治疗具有响应性（R），而14个对RAI治疗没有反应（NR）。我们发现了15个失调的miRNA：其中14个增加，而仅有一个（miR-139-5p）在NR与R肿瘤中表达下降。我们研究了miR-139-5p在碘摄取代谢中的作用。我们在两个原代和五种不老化的甲状腺癌细胞系中过度表达miR-139-5p，并分析了NIS的转录本和蛋白质水平，以及通过碘摄取实验和亚细胞蛋白定位的激活。miR-139-5p过表达细胞内碘水平较高以及细胞膜蛋白质定位的增加发现，支持了这个miRNA在NIS功能调节中的作用。我们的研究提供了miR-139-5p参与碘摄取代谢的证据，并建议其可能作为恢复RAI难治性DTC中碘摄取的治疗靶点。©2023年作者（S）。

Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy.We analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization.The finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function.Our study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC.© 2023. The Author(s).