Skip to main content

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



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.


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


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.


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.


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

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Availability of data and materials

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


  • Al-Khaldi A, Sultan S (2019) The expression of sirtuins, superoxide dismutase, and lipid peroxidation status in peripheral blood from patients with diabetes and hypothyroidism. BMC Endocr Disord 19(1):19

    Article  Google Scholar 

  • Bauer AJ, Wassner AJ (2019) Thyroid hormone therapy in congenital hypothyroidism and pediatric hypothyroidism. Endocrine 66(1):51–62

    CAS  Article  Google Scholar 

  • Boen J, Gevaert AB, De Keulenaer GW, Van Craenenbroeck EM, Segers V (2020) The role of endothelial miRNAs in myocardial biology and disease. J Mol Cell Cardiol 138:75–87

    CAS  Article  Google Scholar 

  • Castello-Waldow TP, Weston G, Ulivi AF, Chenani A, Loewenstein Y, Chen A, Attardo A (2020) Hippocampal neurons with stable excitatory connectivity become part of neuronal representations. PLoS Biol 18(11):e3000928

    CAS  Article  Google Scholar 

  • Chen L, Jia J, Zang Y, Li J, Wan B (2019a) MicroRNA-101 regulates autophagy, proliferation and apoptosis via targeting EZH2 in laryngeal squamous cell carcinoma. Neoplasma 66(4):507–515

    CAS  Article  Google Scholar 

  • Chen XJ, Gong XH, Jie JP, Yu WH, Chen X, Du X, Zhou Q, Wu WJ. Receptor for advanced glycation end products reveals a mechanism regulating thyroid hormone secretion through the SIRT1/Nrf2 pathway. J Cell Biochem 2019b; 120(3): 4582–4598

    CAS  Article  Google Scholar 

  • Cordeiro A, de Souza LL, Oliveira LS, Faustino LC, Santiago LA, Bloise FF, Ortiga-Carvalho TM, Almeida NA, Pazos-Moura CC. Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice. J Endocrinol 2013; 216(2): 181 –181 93

    CAS  Article  Google Scholar 

  • Keshavarzi S, Kermanshahi S, Karami L, Motaghinejad M, Motevalian M, Sadr S (2019) Protective role of metformin against methamphetamine induced anxiety, depression, cognition impairment and neurodegeneration in rat: the role of CREB/BDNF and Akt/GSK3 signaling pathways. Neurotoxicology 72:74–84

    CAS  Article  Google Scholar 

  • Khanjani N, Ahmadzadeh A, Bakhtiari B, Madadizadeh F (2017) The role of season and climate in the incidence of congenital hypothyroidism in Kerman province, Southeastern Iran. J Pediatr Endocrinol Metab 30(2):149–157

    Article  Google Scholar 

  • Ko NY, Chen LR, Chen KH (2020) The role of micro RNA and long-non-coding RNA in osteoporosis. Int J Mol Sci 21(14):4886

    CAS  Article  Google Scholar 

  • Li D, Hao X, Song Y (2018a) Identification of the key micrornas and the miRNA-mRNA regulatory pathways in prostate cancer by bioinformatics methods. Biomed Res Int 2018:6204128

    PubMed  PubMed Central  Google Scholar 

  • Li W, Song D, Sun Y, Lv Y, Lv J (2018b) microRNA-124-3p inhibits the progression of congenital hypothyroidism via targeting programmed cell death protein 6. Exp Ther Med 15(6):5001–5006

    PubMed  PubMed Central  Google Scholar 

  • Li Y, Chen X, Cui Y, Wei Q, Chen S, Wang X (2019) Effects of SIRT1 silencing on viability, invasion and metastasis of human glioma cell lines. Oncol Lett 17(4):3701–3708

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liarte S, Alonso-Romero JL, Nicolas FJ (2018) SIRT1 and estrogen signaling cooperation for breast cancer onset and progression. Front Endocrinol (Lausanne) 9:552

    Article  Google Scholar 

  • Lin CY, Wang SW, Chen YL et al (2017) Brain-derived neurotrophic factor promotes VEGF-C-dependent lymphangiogenesis by suppressing miR-624-3p in human chondrosarcoma cells. Cell Death Dis 8(8):e2964

    CAS  Article  Google Scholar 

  • Liu H, Liu N, Zhao Y et al (2019) Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling. Aging 11(21):9643–9660

    CAS  Article  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    CAS  Article  Google Scholar 

  • Luo Y, Liu W, Tang P et al (2019) miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells. J Exp Clin Cancer Res 38(1):488

    CAS  Article  Google Scholar 

  • Mendes-de-Aguiar CB, Alchini R, Zucco JK et al (2010) Impaired astrocytic extracellular matrix distribution under congenital hypothyroidism affects neuronal development in vitro. J Neurosci Res 88(15):3350–3360

    CAS  Article  Google Scholar 

  • Meng T, Shen S, Li C, Liu X (2020) MicroRNA-1236-3p/translationally controlled tumor protein (TPT1) axis participates in congenital hypothyroidism progression by regulating neuronal apoptosis. Exp Ther Med 19(1):459–466

    CAS  PubMed  Google Scholar 

  • Pei G, Xu L, Huang W, Yin J (2020) The protective role of microRNA-133b in restricting hippocampal neurons apoptosis and inflammatory injury in rats with depression by suppressing CTGF. Int Immunopharmacol 78:106076

    CAS  Article  Google Scholar 

  • Rovet J, Daneman D (2003) Congenital hypothyroidism: a review of current diagnostic and treatment practices in relation to neuropsychologic outcome. Paediatr Drugs 5(3):141–149

    Article  Google Scholar 

  • Samandari-Bahraseman MR, Jahanshahi M, Asadi BS, Elyasi L (2019) Altered Micro-RNA regulation and neuroprotection activity of eremostachys labiosiformis in Alzheimer’s disease model. Ann Neurosci 25(3):160–165

    Article  Google Scholar 

  • Tuli G, Munarin J, Tessaris D, Matarazzo P, Einaudi S, de Sanctis L (2021) Incidence of primary congenital hypothyroidism and relationship between diagnostic categories and associated malformations. Endocrine 71(1):122–129

    CAS  Article  Google Scholar 

  • Van Vliet G, Deladoey J (2014) Diagnosis, treatment and outcome of congenital hypothyroidism. Endocr Dev 26:50–59

    Article  Google Scholar 

  • Wei C, Xu X, Zhu H, Zhang X, Gao Z (2021) Promotive role of microRNA150 in hippocampal neurons apoptosis in vascular dementia model rats. Mol Med Rep 23(4):1

    Article  Google Scholar 

  • Xia XY, Yu YJ, Ye F, Peng GY, Li YJ, Zhou XM (2020) MicroRNA-506-3p inhibits proliferation and promotes apoptosis in ovarian cancer cell via targeting SIRT1/AKT/FOXO3a signaling pathway. Neoplasma 67(2):344–353

    CAS  Article  Google Scholar 

  • Zhang XQ, Song LH, Feng SJ, Dai XM (2019) LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury. Folia Neuropathol 57(4):357–365

    Article  Google Scholar 

  • Zhang X, Li Z, Ji W, Chen X, Gao Q, Li D, Qin H (2020) Influence mechanism of miRNA-144 on proliferation and apoptosis of osteosarcoma cells. Oncol Lett 19(2):1530–1536

    CAS  PubMed  Google Scholar 

  • Zhong G, Long H, Ma S, Shunhan Y, Li J, Yao J (2019) miRNA-335-5p relieves chondrocyte inflammation by activating autophagy in osteoarthritis. Life Sci 226:164–172

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Yuhong Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


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