Department of Urology, Hunan Children's Hospital, Changsha, China.
Cell Mol Biol (Noisy-le-grand). 2024 Jun 5;70(6):122-128. doi: 10.14715/cmb/2024.70.6.19.
Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.
尿道下裂是一种常见的阴茎畸形，属于新生儿期最常见的出生缺陷之一。SRD5A2 可影响男性生殖系统的发育，其在上皮细胞中异常表达。本研究旨在从分子水平探讨 SRD5A2 在尿道下裂发生发展中的作用。通过 Western blot 分析尿道下裂原代细胞中 SRD5A2 的水平，通过双荧光素酶基因报告实验确定其与 miR-1199-5p 的靶向相互作用。通过体外生物学实验验证 SRD5A2 在尿道下裂中的生物学功能。结果显示，尿道下裂原代细胞中 SRD5A2 表达显著上调，miR-1199-5p 表达显著下调。干预 SRD5A2 表达可影响细胞增殖、迁移、侵袭、EMT 及细胞周期相关蛋白的表达。此外，我们发现 SRD5A2 受上游 miR-1199-5p 的调控，并能增强 SRD5A2 对尿道下裂细胞的作用。结论：沉默 SRD5A2 可促进细胞增殖、侵袭和迁移，阻滞细胞周期于 G1 期，同时促进 EMT、细胞周期和细胞增殖相关蛋白的表达。SRD5A2 在尿道下裂细胞中的生物学功能受 miR-1199-5p 调控。SRD5A2 可能是尿道下裂的有效治疗靶点。
