MicroRNA-130a-3p Targets the Androgen-Related Transcription Factor MAFB: Effects on Proliferation, Migration, Apoptosis, and Cell Cycle in Hypospadias.

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.