Spatiotemporal pattern analysis of transcription factor 4 in the developing anorectum of the rat embryo with anorectal malformations

Zhang, Tao; Bai, Yu; Wang, Da Jia; Jia, Hui; Yuan, Zheng Wei; Wang, Wei Lin

doi:10.1007/s00384-009-0705-3

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…27 Previous studies have shown that, despite an unclear and complex multifactorial etiology, maldevelopment of the urorectal septum and failure of fusion with the cloacal membrane may underlie ARM. 28 Acting as special types of noncoding RNA molecules, circRNAs can regulate gene expression via miRNA sponges, which indicates that circRNAs may exert a regulatory function in different diseases. 29 However, the expression of circRNAs and their potential regulatory role in ARM have not been addressed so far.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, patients with these abnormalities always have severe and long‐term medical problems . Previous studies have shown that, despite an unclear and complex multifactorial etiology, maldevelopment of the urorectal septum and failure of fusion with the cloacal membrane may underlie ARM . Acting as special types of noncoding RNA molecules, circRNAs can regulate gene expression via miRNA sponges, which indicates that circRNAs may exert a regulatory function in different diseases .…”

Section: Discussionmentioning

confidence: 99%

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Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations

Liú

Jia

et al. 2019

J of Cellular Biochemistry

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Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have regulatory functions in varieties of diseases. The purpose of this study was to investigate the potential role of circRNAs in anorectal malformations (ARM). With sequencing analysis, 78 circRNAs were identified to be differentially expressed on gestational day (GD) 19 in ARM and normal anorectal tissues, including 41 upregulated and 37 downregulated circRNAs. Among the downregulated circRNAs, rno_circ_0004002 was selected as the candidate circRNA. Functionally, silencing of rno_circ_0004002 was correlated with suppression of proliferation, and promotion of apoptosis and epithelial‐mesenchymal transition (EMT) in anorectal development. For the mechanism investigation, bioinformatic prediction and luciferase reporter assay revealed that rno_circ_0004002 was proved to be a sponge of miR‐342‐5p, and miR‐342‐5p could target 3'‐UTR of Wnt3a to negatively regulate its expression. The quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results showed that the expression of miR‐342‐5p was significantly increased in ARM anorectal tissues compared with normal tissues on GD19 and GD21, and the expression of Wnt3a demonstrated the opposite on GD21. In addition, rescue assays disclosed that miR‐342‐5p inhibitor could reverse the role of rno_circ_0004002 knockdown on the repression of anorectal development. In summary, our study shed light on the regulatory mechanism of rno_circ_0004002 in cell proliferation, apoptosis, and EMT via sponging miR‐342‐5p, which downregulated the Wnt3a expression in anorectal development. We also suggested that GD19 and GD21 was the crucial time in the progression of ARM, and rno_circ_0004002/miR‐342‐5p/Wnt3a might serve as potential therapeutic targets for ARM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations

Liú

Jia

et al. 2019

J of Cellular Biochemistry

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“…ETU-induced ARMs in rat embryos has been previously employed to study the morphological changes of ARMs by several groups, including our laboratory ( Qi, Beasley & Frizelle, 2002 ; Bai et al, 2004 ; Mandhan et al, 2006a ; Mandhan et al, 2006b ; Zhang et al, 2009 ; Wang et al, 2009 ; Tang et al, 2014a ; Tang et al, 2014b ; Zhang et al, 2015 ). In this study, expression of Wif1 in the anorectum showed differences in spatial distribution between normal and ARM embryos.…”

Section: Discussionmentioning

confidence: 99%

Expression pattern of Wif1 and β-catenin during development of anorectum in fetal rats with anorectal malformations

Tang

Zhang

et al. 2018

PeerJ

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PurposeThis study was performed to investigate the expression pattern of Wnt inhibitory factor 1 (Wif1) and β-catenin during anorectal development in normal and anorectal malformation (ARM) embryos and the possible role of Wif1 and β-catenin in the pathogenesis of ARM.MethodsARM was induced with ethylenethiourea on the 10th gestational day in rat embryos. Cesarean deliveries were performed to harvest the embryos. The expression pattern of Wif1 and β-catenin protein and mRNA was evaluated in normal rat embryos (n = 288) and ARM rat embryos (n = 306) from GD13 to GD16 using immunohistochemical staining, Western blot, and real time RT-PCR.ResultsImmunohistochemical staining revealed that in normal embryos Wif1 was constantly expressed in the cloaca from GD13 to GD16. On GD13 and GD14, Wif1-immunopositive cells were extensively expressed in the cloaca. On GD15, the expression of Wif1 were mainly detected on the very thin anal membrane. In ARM embryos, the epithelium of the hindgut and urorectal septum demonstrated faint immunostaining for Wif1 from GD14 to GD16. Western blot and real time RT-PCR revealed that Wif1 and β-catenin protein and mRNA expression level was significantly decreased in the ARM groups compared with the normal group on GD14 and GD15 (p < 0.05).ConclusionsThis study demonstrated that the expression pattern of Wif1 and β-catenin was disrupted in ARM embryos during anorectal morphogenesis, which demonstrated that downregulation of Wif1 and β-catenin at the time of cloacal separation into the primitive rectum and urogenital septum might related to the development of ARM.

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“…Up to now, the etiology of ARMs remains unknown, although several evidences indicated that genetic component involved in the pathogenesis2. Recent studies in animal models with ARMs have greatly enhanced our knowledge in this multifaceted developmental process3,4, which has provided clues to genes and pathways that may be operating in human diseases and in most cases, mutations in the human orthologs give rise to similar or related phenotypes. During the essential period of hindgut development, considerable signaling molecules participated in the embryogenesis of the anorectum, including Wnt5a5,6, Tcf44, Sonic hedgehog (Shh)7,8, Fibroblast growth factor 10(Fgf10)9, Hoxa-13 and Hoxd-1310.…”

Section: Introductionmentioning

confidence: 99%

Mutations and Down-Regulation of CDX1 in Children with Anorectal Malformations

Zhang¹,

Tang²,

Wang³

et al. 2013

Int. J. Med. Sci.

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Background: Anorectal malformations (ARMs) represent a variety of congenital disorders that involve abnormal termination of the anorectum. This study was to reveal relation between CDX1 and human ARMs phenotypes.Methods: 108 Chinese patients and 120 Chinese controls were included in this study. We analyzed the relation between two by PCR, qRT-PCR, western blot and immunofluorescence.Results: Four heterozygous mutations in CDX1 gene were identified in ARMs patients (3.7%, 4/108), no found in controls. CDX1 protein expression was significantly decreased in the ARMs compared with the control anorectum. All samples analyzed in ARMs group exhibited down-regulated CDX1 mRNA expression in comparison to matched normal group, demonstrated significant differences statistically.Conclusion: The findings represented the relation between CDX1 mutations and CDX1 genotype. Furthermore, it was suggested that the downregulation of CDX1 might be related to the development of ARMs.

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Spatiotemporal pattern analysis of transcription factor 4 in the developing anorectum of the rat embryo with anorectal malformations

Abstract: These data implied that the downregulation of Tcf4 at the time of cloacal separation into rectum and urethra might be related to the development of ARM.

Cited by 8 publications

References 22 publications

Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations

Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations

Expression pattern of Wif1 and β-catenin during development of anorectum in fetal rats with anorectal malformations

Mutations and Down-Regulation of CDX1 in Children with Anorectal Malformations

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