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FOXA1、DUSP6和HA117在先天性巨结肠症结肠段中的差异表达。

Differential expression of FOXA1, DUSP6, and HA117 in colon segments of Hirschsprung's disease.

作者信息

Luo Yuanyuan, Li Shuangshuang, Teng Yinping, Wang Ning, Li Li, Liu Hang, Jin Xianqing

机构信息

Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University Yuzhong District, Chongqing 400014, P. R. China ; Department of Neonatal Gastrointestinal Surgery, Children's Hospital of Chongqing Medical University Yuzhong District, Chongqing 400014, P. R. China.

出版信息

Int J Clin Exp Pathol. 2015 Apr 1;8(4):3979-86. eCollection 2015.

Abstract

OBJECTIVE

To describe the expression profiles of FOXA1, DUSP6, and HA117 in different portions of the colon of patients diagnosed with Hirschsprung's disease (HSCR).

METHODS

Colon specimens were collected from 34 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Levels of FOXA1, DUSP6, and HA117 RNA were evaluated by real-time PCR. Levels of FOXA1 and DUSP6 protein were analyzed by immunohistochemistry and Western blotting.

RESULTS

The levels of FOXA1 and DUSP6 RNA were significantly lower in the stenotic segment compared to proximal anastomosis (P < 0.05). The level of HA117 RNA was significantly higher in the stenotic segment compared to proximal anastomosis (P < 0.05). In proximal anastomosis, FOXA1 and DUSP6 were both expressed at the protein level in ganglion cells and nerve fibers between the circular and longitudinal muscles. In the stenotic segments, positive staining for FOXA1 and DUSP6 was diminished. The levels of FOXA1 and DUSP6 protein were significantly lower in the stenotic segment compared to proximal anastomosis (P < 0.05).

CONCLUSION

Suppression of the FOXA1/DUSP6 signaling pathway may contribute to the development of HSCR. LncRNA HA117 may have an anti-differentiation function, and play a pivotal role in the progression of HSCR.

摘要

目的

描述叉头框蛋白A1(FOXA1)、双特异性磷酸酶6(DUSP6)和长链非编码RNA HA117(HA117)在诊断为先天性巨结肠(HSCR)患者结肠不同部位的表达谱。

方法

收集34例HSCR患者的结肠标本,分为3个节段:近端吻合口、扩张段和狭窄段。通过实时定量聚合酶链反应(PCR)评估FOXA1、DUSP6和HA117 RNA水平。通过免疫组织化学和蛋白质免疫印迹法分析FOXA1和DUSP6蛋白水平。

结果

与近端吻合口相比,狭窄段FOXA1和DUSP6 RNA水平显著降低(P < 0.05)。与近端吻合口相比,狭窄段HA117 RNA水平显著升高(P < 0.05)。在近端吻合口,FOXA1和DUSP6在神经节细胞以及环行肌和纵行肌之间的神经纤维中均有蛋白水平表达。在狭窄段,FOXA1和DUSP6的阳性染色减弱。与近端吻合口相比,狭窄段FOXA1和DUSP6蛋白水平显著降低(P < 0.05)。

结论

FOXA1/DUSP6信号通路的抑制可能有助于HSCR的发生发展。长链非编码RNA HA117可能具有抗分化功能,并在HSCR进展中起关键作用。

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