Yin Guang, Kong Wencheng, Zheng Sixin, Shan Yuqiang, Zhang Jian, Ying Rongchao, Wu Hao
Department of General Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.
Oncol Lett. 2021 Apr;21(4):283. doi: 10.3892/ol.2021.12544. Epub 2021 Feb 12.
The aim of the present study was to determine the expression and diagnostic value of exosomal miR-130a-3p in the serum of patients with differentiated thyroid cancer (DTC). Exosomes were isolated from the serum of patients with DTC and were identified using transmission electron microscopy. A novel exosomal miRNA, miR-130a-3p, was found to be significantly decreased in the serum of patients with DTC compared with those with benign thyroid tumors and healthy controls. Further study revealed that exosomal miR-130a-3p was correlated with the malignant characteristics of DTC, including tumor diameter, lymph node metastasis (LNM) and higher TNM stage. Receiver operating characteristic curve analysis demonstrated that the area under the curve of exosomal miR-130a-3p was better compared with that of TgAb and Tg in patients with DTC. More importantly, the combined use of exosomal miR-130a-3p, TgAb and Tg significantly enhanced the sensitivity and specificity, indicating that exosomal miR-130a-3p is a sensitive biomarker for DTC. A dual luciferase reporter assay indicated that insulin-like growth factor (IGF)-1 was a target gene of miR-130a-3p. Pearson's correlation analysis revealed a negative correlation between serum IGF-1 and serum exosomal miR-130a-3p levels. More importantly, exosomes from patients with DTC increased the expression of IGF-1 and p-PI3K/p-AKT, but these effects were abolished by siRNA targeting IGF-1 in TPC-1 cells. Taken together, the findings of the present study indicated that reduced exosomal miR-130a-3p levels were associated with the risk of DTC and may be used as a biomarker for the diagnosis of DTC.
本研究的目的是确定外泌体miR-130a-3p在分化型甲状腺癌(DTC)患者血清中的表达及其诊断价值。从DTC患者血清中分离出外泌体,并通过透射电子显微镜进行鉴定。发现一种新型外泌体微小RNA(miRNA),即miR-130a-3p,在DTC患者血清中的表达与良性甲状腺肿瘤患者及健康对照相比显著降低。进一步研究表明,外泌体miR-130a-3p与DTC的恶性特征相关,包括肿瘤直径、淋巴结转移(LNM)及更高的TNM分期。受试者工作特征曲线分析表明,在DTC患者中,外泌体miR-130a-3p的曲线下面积优于甲状腺球蛋白抗体(TgAb)和甲状腺球蛋白(Tg)。更重要的是,联合使用外泌体miR-130a-3p、TgAb和Tg可显著提高敏感性和特异性,表明外泌体miR-130a-3p是DTC的敏感生物标志物。双荧光素酶报告基因检测表明胰岛素样生长因子(IGF)-1是miR-130a-3p的靶基因。Pearson相关性分析显示血清IGF-1与血清外泌体miR-130a-3p水平呈负相关。更重要的是,DTC患者的外泌体增加了IGF-1和磷酸化磷脂酰肌醇-3激酶(p-PI3K)/磷酸化蛋白激酶B(p-AKT)的表达,但在TPC-1细胞中,靶向IGF-1的小干扰RNA(siRNA)消除了这些作用。综上所述,本研究结果表明外泌体miR-130a-3p水平降低与DTC风险相关,可能用作DTC诊断的生物标志物。