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20 July 2018 : Animal Research  

miRNA-125b-5p Suppresses Hypothyroidism Development by Targeting Signal Transducer and Activator of Transcription 3

Liu Xiu12ABCDEF, Qian Xing1AB, Jinyuan Mao1B, Huakun Sun1B, Weiping Teng1AEG*, Zhongyan Shan1C

DOI: 10.12659/MSM.907510

Med Sci Monit 2018; 24: ANS5041-5049

Abstract

BACKGROUND: A deficiency of maternal thyroid hormones (THs) during pregnancy has severe impacts on fetal brain development. Neural stem cells (NSCs) are major targets of THs and provided a powerful model to explore the underlying mechanism of THs during brain development. Although miRNA-125 might be associated with the NSCs differentiation, the relationship between miR-125 and hypothyroidism (HypoT) development remains unclear.

MATERIAL AND METHODS: In our study, we screened a differentially expressed gene miR-125b-5p from brain between euthyroid (EuT) and HypoT rats. In vitro, we employed anion exchange resin to remove THs to stimulate HypoT. QRT-PCR and Western blot were used to examine the expression of signal transducer and activator of transcription 3 (Stat3). The relationship between miR-125b-5p and Stat3 was detected via a dual-luciferase assay.

RESULTS: QRT-PCR results showed that the level of miR-125b-5p in HypoT rat brains was significantly suppressed, suggesting some relationship between miR-125b-5p and HypoT. In C17.2, miR-125b-5p promoted cell differentiation into neurons by regulating the expression of tubulin beta chain 3 (TUBB3) and glial fibrillary acid protein (GFAP). QRT-PCR and Western blot results revealed that miR-125b-5p mimic modulated the contents of total Stat3 and p-Stat3. A dual-luciferase assay showed that miR-125b-5p negatively regulated the expression of Stat3 by binding with the first site in 3’ UTR of Stat3.

CONCLUSIONS: These results revealed Stat3 is a new target of miR-125b-5p and revealed the mechanism of miR-125b-5p suppressing HypoT development. These findings provide a new target for HypoT therapy.

Keywords: Hypothyroidism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750