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Published on: May 16, 2012
MicroRNA-130a-3p Targets the Androgen-Related Transcription Factor MAFB: Effects on Proliferation, Migration,
Jiaxin Zhou1,2, Yixuan Wang1,2, Zhicheng Zhang1,2
1Department of Urology Children's Hospital of Chongqing Medical University National Clinical Research Center for Children and Adolescents' Health and Diseases Ministry of Education Key Laboratory of Child Development and Disorders Chongqing China.
Abstract:
Hypospadias is among the most frequent congenital malformations of the male genitalia. The expression of V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), a transcription factor within the androgen signaling pathway, is closely correlated with the etiology of this condition. From an epigenetic perspective, this study investigated the role of microRNA-130a-3p (miR-130a-3p) in regulating MAFB during hypospadias pathogenesis. Clinical foreskin samples from hypospadias children and the dioctyl phthalate (DEHP)-induced mouse genital tubercle tissues were analyzed. The expression levels of miR-130a-3p and MAFB were detected by qRT-PCR and western blot. In vitro, miR-130a-3p was modulated in HS68 cells; CCK-8, scratch assay, western blot, flow cytometry, and dual-luciferase assay were used to assess its effects and targeting of MAFB. Our study demonstrated that miR-130a-3p targeted and suppressed MAFB expression. This suppression inhibited cellular proliferation and migration and reduced Vimentin mRNA expression. Cell cycle distribution was disrupted, marked by Gap 1 phase increase and Synthesis phase reduction, and the cell apoptosis rate increased. Cyclin-dependent kinase 2 (CDK2), Cyclin E1, and Proliferating Cell Nuclear Antigen (PCNA) were downregulated. miR-130a-3p targets and inhibits MAFB expression, disrupting the normal processes of cell proliferation, migration, cell apoptosis, and cell cycle progression, ultimately leading to the development of hypospadias.
Insights
MicroRNA-130a-3p (miR-130a-3p) targets and suppresses V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) expression. This disruption in gene regulation contributes to hypospadias development by affecting cell growth and apoptosis.
Area of Science:
- Developmental Biology
- Epigenetics
- Molecular Biology
Background:
- Hypospadias is a common congenital malformation affecting male genitalia.
- V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) expression is linked to hypospadias etiology.
- Epigenetic regulation, specifically microRNAs, may play a role in this condition.
Purpose of the Study:
- To investigate the role of microRNA-130a-3p (miR-130a-3p) in regulating MAFB during hypospadias pathogenesis.
- To explore the epigenetic mechanisms underlying hypospadias development.
Main Methods:
- Analysis of clinical foreskin and DEHP-induced mouse genital tubercle tissues.
- qRT-PCR and Western blot to quantify miR-130a-3p and MAFB expression.
- In vitro studies using HS68 cells with assays for proliferation, migration, cell cycle, apoptosis, and dual-luciferase reporter assay.
Main Results:
- miR-130a-3p was found to directly target and suppress MAFB expression.
- Suppression of MAFB by miR-130a-3p inhibited cell proliferation and migration, and reduced Vimentin.
- Cell cycle progression was disrupted, apoptosis increased, and key regulatory proteins (CDK2, Cyclin E1, PCNA) were downregulated.
Conclusions:
- miR-130a-3p acts as a negative regulator of MAFB in hypospadias pathogenesis.
- Dysregulation of miR-130a-3p and MAFB impacts critical cellular processes, contributing to hypospadias.
- This study highlights a novel epigenetic pathway involved in male genital development defects.
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