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Exosomal miR-130a-3p promotes the progression of differentiated thyroid cancer by targeting insulin-like growth factor 1
Authors:Guang Yin  Wencheng Kong  Sixin Zheng  Yuqiang Shan  Jian Zhang  Rongchao Ying  Hao Wu
Affiliation:Department of General Surgery, Affiliated Hangzhou First People''s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Abstract: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.
Keywords:exosome   miR-130a-3p   differentiated thyroid cancer   serum
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