Background

Congenital hypospadias is a common congenital malformation of the urinary system in male children. However, the role of circRNA in congenital hypospadias remains unknown.

Methods

Differentially expressed circRNAs and mRNAs were identified by RNA sequencing. GO and KEEG analysis were performed to uncover the key function and pathways. The interaction networks were constructed and analyzed by competing endogenous (ce)RNA analysis. Immunohistochemistry (IHC) and qRT-PCR were used to detect the expressions of androgen receptor (AR) and hsa_circ_0000417 in normal and hypospadias tissues. Further, the correlation between hsa_circ_0000417 and other clinical indicators were calculated.

Results

Compared with normal foreskin tissues, 1329 circRNAs and 978 mRNAs were significantly upregulated, 3176 circRNAs and 614 mRNAs were significantly downregulated in hypospadias tissues, respectively. MAPK and PI3K-Akt signaling pathways play important roles in congenital hypospadias. The expression of AR and hsa_circ_0000417 in 68 hypospadias tissues was significantly lower than that in 68 normal foreskin tissues (P < 0.05). The expression of the AR, as analyzed using IHC, was consistent with the qPCR results. A significant correlation was noted between the expression of AR and hsa_circ_0000417 in 68 clinical samples (P < 0.05). Furthermore, the expression level of hsa_circ_0000417 was associated with the incidence of other diseases and the location of the hypospadias site (P < 0.05). Expression of hsa_circ_0000417 was significantly downregulated in hypospadias patients without other diseases (P < 0.05).

Conclusion

Hsa_circ_0000417 may regulate the expression of AR, and the expression of hsa_circ_0000417 in normal foreskin tissues is associated with the occurrence of hypospadias.

中文翻译：

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hsa_circ_0000417通过调节AR参与尿道下裂的发展

背景

先天性尿道下裂是男性儿童泌尿系统常见的先天性畸形。然而，circRNA 在先天性尿道下裂中的作用仍然未知。

方法

通过RNA测序鉴定差异表达的circRNA和mRNA。进行 GO 和 KEEG 分析以揭示关键功能和途径。通过竞争性内源 (ce) RNA 分析构建和分析相互作用网络。免疫组化（IHC）和qRT-PCR检测正常和尿道下组织中雄激素受体（AR）和hsa_circ_0000417的表达。此外，还计算了 hsa_circ_0000417 与其他临床指标之间的相关性。

结果

与正常包皮组织相比，尿道下组织中1329个circRNAs和978个mRNAs显着上调，3176个circRNAs和614个mRNAs显着下调。MAPK 和 PI3K-Akt 信号通路在先天性尿道下裂中起重要作用。AR和hsa_circ_0000417在68例尿道下裂组织中的表达明显低于68例正常包皮组织（P  < 0.05）。使用 IHC 分析的 AR 的表达与 qPCR 结果一致。在 68 个临床样本中，AR 的表达与 hsa_circ_0000417 之间存在显着相关性（P  < 0.05）。此外，hsa_circ_0000417的表达水平与其他疾病的发病率和尿道下裂部位的位置有关。P  < 0.05)。hsa_circ_0000417的表达在没有其他疾病的尿道下裂患者中显着下调（P  < 0.05）。

结论

Hsa_circ_0000417可能调控AR的表达，正常包皮组织中hsa_circ_0000417的表达与尿道下裂的发生有关。