Inhibition of microRNA-875-5p promotes radioiodine uptake in poorly differentiated thyroid carcinoma cells by upregulating sodium-iodide symporter (Retracted article. See vol. 45, pg. 2025, 2022)
Inhibition of microRNA-875-5p promotes radioiodine uptake in poorly differentiated thyroid carcinoma cells by upregulating sodium-iodide symporter (Retracted article. See vol. 45, pg. 2025, 2022)
复制标题
DOI：
10.1007/s40618-019-01125-3
复制
发表时间：
2019-10-14
影响因子：
5.4
通讯作者：
Dong, J.
中科院分区：
文献类型：
--
作者：
Tang, Y.;Meng, X.;Dong, J.
背景和目的低分化甲状腺癌（PDTC）是一种内分泌恶性肿瘤，由于其放射性碘摄取有限，治疗具有挑战性。microRNAs （miRNAs或miRs）已被证明在治疗包括PDTC在内的许多类型的肿瘤中都是有用的。本研究旨在评估miR-875-5p对PDTC放射性碘摄取的潜在影响，并阐明其潜在机制。方法采用RT-qPCR检测miR-875-5p和碘化钠同调体（NIS）在组织和细胞系中的表达。通过硅分析预测miR-875-5p与NIS的结合关系，并通过双荧光素酶报告基因试验验证。将一系列miR-875-5p模拟物、miR-875-5p抑制剂、针对NIS的shRNA和过表达的NIS质粒导入PDTC细胞。然后，我们分别通过CCK-8实验、克隆生成实验、流式细胞术和伽马计数器来评估每个PDTC样品的细胞活力、集落形成、凋亡和放射性碘摄取。结果miR-875-5p在DTC组织和PDTC细胞系中高表达，而NIS低表达。NIS被证实是miR-875-5p的靶基因。研究发现，miR-875-5p上调可诱导PDTC细胞增殖，并通过下调NIS减少细胞凋亡和放射性碘摄取。在体内原位模型中，miR-875-5p的增强导致甲状腺肿瘤中NIS表达和放射性碘摄取的减少。总之，本研究结果表明，miR-875-5p表达下调可促进其靶基因NIS增加PDTC的放射性碘摄取，从而构成PDTC的预防策略。
Background and Aim Poorly differentiated thyroid carcinoma (PDTC) is an endocrine malignancy that is challenging to treat due to its limited radioiodine uptake. microRNAs (miRNAs or miRs) have been shown to be useful in treating many types of tumors, including PDTC. This study aims to evaluate the potential effect of miR-875-5p on the radioiodine uptake of PDTC and to clarify the underlying mechanisms. Methods Expression of miR-875-5p and sodium-iodide symporter (NIS) in tissues and cell lines was determined using RT-qPCR. The binding relationship between miR-875-5p and NIS was predicted through in silico analysis and verified by dual-luciferase reporter gene assay. A series of miR-875-5p mimic, miR-875-5p inhibitor, shRNA against NIS, and overexpressed NIS plasmids were introduced into PDTC cells. We then evaluated the cell viability, colony formation, apoptosis, and radioiodine uptake of each PDTC sample via CCK-8 assay, clonogenic assay, flow cytometry, and gamma counter, respectively. Results miR-875-5p was found to be highly expressed, but NIS was poorly expressed in DTC tissues and PDTC cell lines. NIS was verified to be a target gene of miR-875-5p. Upregulation of miR-875-5p was found to induce PDTC cell proliferation, and reduce apoptosis and radioiodine uptake in vitro through down-regulation of NIS. In an in vivo orthotopic model, the enhancement of miR-875-5p led to the reduction of NIS expression and radioiodine uptake in the thyroid tumors. Conclusions Altogether, the findings of the current study suggest that down-regulated miR-875-5p expression could promote its target gene NIS to increase radioiodine uptake in PDTC, constituting a preventive strategy against PDTC.