miR-139-5p 在碘难治性甲状腺癌中的作用。

The role of miR-139-5p in radioiodine-resistant thyroid cancer.

机构信息

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

出版信息

J Endocrinol Invest. 2023 Oct;46(10):2079-2093. doi: 10.1007/s40618-023-02059-7. Epub 2023 Mar 18.

DOI:10.1007/s40618-023-02059-7

PMID:36933170

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10514163/

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

放射性碘 I-131（RAI）是分化型甲状腺癌（DTC）的首选治疗方法。由于碘代谢成分（尤其是钠/碘转运体[NIS]）的表达/功能丧失，5%-15%的 DTC 患者对 RAI 产生耐药性。我们寻找与 RAI 耐药性 DTC 相关的 miRNA 谱，以鉴定可能成为红色分化治疗潜在靶点的新型生物标志物。

方法

我们分析了 26 例 DTC 组织中 754 种 miRNA 的表达：12 例对 RAI 治疗有反应（R），14 例无反应（NR）。我们确定了 15 个失调的 miRNA：14 个上调，而仅一个（miR-139-5p）在 NR 与 R 肿瘤中下调。我们研究了 miR-139-5p 在碘摄取代谢中的作用。我们在两种原代和五种永生化甲状腺癌细胞系中转染 miR-139-5p，通过碘摄取测定和亚细胞蛋白定位分析 NIS 的转录和蛋白水平及其激活。