NIS is a potent iodide transporter encoded by the SLC5A5 gene. Its expression is reduced in papillary thyroid carcinoma (PTC). In this study we analyzed the impact of miR-181a-5p on NIS expression in the context of PTC. We used real-time PCR to analyze the expression of SLC5A5 and miR-181a-5p in 49 PTC/normal tissue pairs. Luciferase assays and mutagenesis were performed to confirm direct binding of miR-181a-5p to the 3′UTR of SLC5A5 and identify the binding site. The impact of modulation of miR-181a-5p using appropriate plasmids on endogenous NIS and radioactive iodine accumulation was verified. We confirmed downregulation of SLC5A5 and concomitant upregulation of miR-181a-5p in PTC. Broadly used algorithms did not predict the binding site of miR-181a-5p in 3′UTR of SLC5A5, but we identified and confirmed the binding site through mutagenesis using luciferase assays. In MCF7 and HEK293-flhNIS cell lines, transfection with mir-181a-expressing plasmid decreased endogenous SLC5A5, whereas silencing of miR-181a-5p increased it. We observed similar tendencies in protein expression and radioactive iodine accumulation. This study shows for the first time that miR-181a-5p directly regulates SLC5A5 expression in the context of PTC and may decrease efficacy of radioiodine treatment. Accordingly, miR-181a-5p may serve as an emerging target to enhance the efficacy of radioactive iodine therapy.

Distal hereditary motor neuropathies are a heterogeneous group of rare, genetically determined neuromuscular disorders. Distal hereditary motor neuropathy type IIB is an autosomal dominant disorder, and the onset of symptoms is observed in adulthood. Mutation refers to heat shock protein 27, also known as heat shock protein beta-1. The main symptoms of distal hereditary motor neuropathy type IIB are muscular atrophy and paresis of distal limb muscles. In this article, we present the first Polish case of familial late onset distal hereditary neuropathy type IIB with a T151I mutation (p.Thr151Ile) in one allele of the heat shock protein 27 gene. The first symptoms of the disease in our patients began around the age of 60.

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