Identification of Circulating Exosomal microRNAs Associated with Radioiodine Refractory in Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) has a favorable prognosis, but a fraction of cases show progressive behaviors, becoming radioiodine refractory (RAIR) PTC. To explore circulating exosomal microRNAs (miRNAs) associated with RAIR PTC, the miRNA profiles in exosomes from parental and induced RAIR cell lines were firstly identified with a next-generation sequencing technique. The Na(+)/I(−) symporter (NIS) related miRNAs were then validated by quantitative real-time PCR (qRT-PCR) in plasma of PTC patients with non-(131)I-avid metastases and those with (131)I-avid metastases. The regulation of exosomal miRNAs on NIS were also verified. We identified that miR-1296-5p, upregulation in exosomes from RAIR cell lines, and the plasma of patients with RAIR PTC achieved the largest areas under the curve (AUC) of 0.911 and that it is an independent risk factor for RAIR PTC. In addition, miR-1296-5p was abundantly detected in the tissue of RAIR PTC and can directly target downstream gene of NIS. Taken together, our findings suggested that circulating exosomal miRNAs, particularly miR-1296-5p, may be involved in the pathogenesis of RAIR PTC by directly targeting NIS.