RGD Reference Report - Downregulation of MicroRNA-494 inhibits the TGF-β1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L. - Rat Genome Database

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Downregulation of MicroRNA-494 inhibits the TGF-β1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

Authors: Tian, Run-Hui  Guo, Kai-Min  Han, Guang-Hong  Bai, Yang 
Citation: Tian RH, etal., Exp Mol Pathol. 2020 Aug;115:104452. doi: 10.1016/j.yexmp.2020.104452. Epub 2020 May 13.
RGD ID: 156431051
Pubmed: PMID:32413360   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yexmp.2020.104452   (Journal Full-text)


BACKGROUND: Hypospadias, as a congenital disorder of the urethra, is the second most common birth abnormality of the male reproductive system. This study primarily investigates the effects of microRNA-494 (miR-494) on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and on the development of hypospadias by binding to neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4L).
METHODS: We induced a mouse model of hypospadias through di-(2-ethylhexyl) phthalate treatment. The underlying regulatory mechanisms of miR-494 in this model were analyzed upon treatment of miR-494 mimic, miR-494 inhibitor, or small interfering RNA against Nedd4L in urethral epithelial cells isolated from mice with hypospadias. We then verified the binding site between miR-494 and Nedd4L and applied a gain- and loss-of-function approach to determine the effects of miR-494 on cell proliferation, cycle distribution, and apoptosis.
RESULTS: Male mice with hypospadias exhibited significantly higher miR-494 expression and lower Nedd4L expression in urethral tissues than normal male mice. Nedd4L was verified as a target gene of miR-494. Treatment with miR-494 inhibitor suppressed the activation of the TGF-β1/Smads signaling pathway, whereas down-regulation of miR-494 exerted protective effects on urethral epithelial cells by impeding cell proliferation and inducing cell apoptosis.
CONCLUSIONS: The study indicates that downregulation of miR-494 inhibits the TGF-β1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MIR494Humanhypospadias  ISOMir494 (Mus musculus)RNA:increased expression:urethraRGD 
Mir494Mousehypospadias  IEP RNA:increased expression:urethraRGD 
Mir494Rathypospadias  ISOMir494 (Mus musculus)RNA:increased expression:urethraRGD 
NEDD4LHumanhypospadias  ISONedd4l (Mus musculus)protein:decreased expression:urethraRGD 
Nedd4lRathypospadias  ISONedd4l (Mus musculus)protein:decreased expression:urethraRGD 
Nedd4lMousehypospadias  IEP protein:decreased expression:urethraRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir494  (microRNA 494)
Nedd4l  (NEDD4 like E3 ubiquitin protein ligase)

Genes (Mus musculus)
Mir494  (microRNA 494)
Nedd4l  (neural precursor cell expressed, developmentally down-regulated gene 4-like)

Genes (Homo sapiens)
MIR494  (microRNA 494)
NEDD4L  (NEDD4 like E3 ubiquitin protein ligase)


Additional Information