Biomarker potential of serum microRNAs in thyroid nodules patients residing in high water iodine areas

The incidence of thyroid nodules is notably higher in high iodine areas. Currently, there is no study on the relationship between microRNAs and benign thyroid nodules. In this study, accompanied by urinary, blood and water iodine detection, we analyzed microRNA expression profiles through RNA sequencing in patients with benign thyroid nodules and healthy controls from iodine deficiency, adequate and high areas, respectively. Subsequently, specific microRNAs found in high iodine areas and their target genes involved in iodine metabolism were validated using Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). Univariate and multivariate logistic regression analyses revealed that elevated blood iodine levels, upregulated expression of hsa-miR-185-5p, downregulated expression of hsa-miR-21-5p, and enlarged thyroid volume are independent risk factors for thyroid nodules. Furthermore, a strong negative correlation was observed between hsa-miR-185-5p expression and monocarboxylate transporter 8 (MCT8) mRNA expression. For diagnosing high iodine-associated thyroid nodules, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) values for MCT8 mRNA exceeded 0.9, and those for hsa-miR-185-5p and hsa-miR-28-3p were approximately 0.8. Furthermore, the combination of MCT8 mRNA alongside hsa-miR-185-5p and hsa-miR-28-3p was identified as the most effective diagnostic indicator, achieving AUC values greater than 0.99. In conclusion, elevated blood iodine levels and hsa-miR-185-5p-MCT8 axis may play critical roles in high iodine-related thyroid nodules. Additionally, the combining MCT8 mRNA with hsa-miR-185-5p and hsa-miR-28-3p could serve as potential biomarkers for diagnosing high iodine-related thyroid nodules. These findings provide a foundation for future biological therapy as well as monitoring strategies study related to high iodine-associated thyroid nodules.