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The role of miRNA-624-5p in congenital hypothyroidism and its molecular mechanism by targeting SIRT1

Abstract

Background

Accumulating reports evidenced that congenital hypothyroidism (CH) is a kind of endocrine diseases caused by thyroid hormone imperfection. MicroRNAs (miRNAs) were confirmed to exhibit protective functions in CH progression. However, the functions and latent mechanism of microRNA-624-5p (miR-624-5p) in CH remains unknown.

Objective

This report was designed to illustrate the potential molecular mechanisms of miR-624-5p on CH.

Methods

Rats were induced by 50 mg/day propylthiouracil to conduct CH models. Free thyroxine (fT4) and thyroid-Stimulating hormone (TSH) concentrations were measured to confirm CH model conduction. The direct target of miR-624-5p was predicted and verified by Starbase and dual luciferase reporter assay. Besides, the levels of miR-624-5p and sirtuin1 (SIRT1) in hippocampus or hippocampal neuronal cells were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assays. Then CH rat behaviors were evaluated using open field test (OFT) and forced swim test (FST). Furthermore, neuronal cells viability and apoptosis were checked using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry.

Results

qRT-PCR assay suggested that miR-624-5p was up-regulated and SIRT1 was low-expressed in hippocampus tissues of CH rats. SIRT1 was a direct target of miR-624-5p. MiR-624-5p inhibitor signally enhanced fT4 levels and reduced TSH levels in the plasma of CH rats, and improved CH rat depressive behaviors by targeting SIRT1. Moreover, our data also revealed that miR-624-5p inhibitor increased cell viability and reduced apoptotic neuronal cells, which was reversed by silencing of SIRT1.

Conclusions

Taken together, this research demonstrated that miR-624-5p serves as a promising target for CH treatment.

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Availability of data and materials

All datasets used and/or generated during the current study are available from the corresponding author on reasonable request.

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Correspondence to Yuhong Wang.

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Wu, W., Cao, X. & Wang, Y. The role of miRNA-624-5p in congenital hypothyroidism and its molecular mechanism by targeting SIRT1. Genes Genom 44, 1137–1147 (2022). https://doi.org/10.1007/s13258-021-01171-3

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  • DOI: https://doi.org/10.1007/s13258-021-01171-3

Keywords

  • miRNA-624-5p
  • Neuronal cell
  • Congenital hypothyroidism
  • SIRT1