Validation and in silico function prediction of circtial1 as a novel marker of abnormal lung development in nitrofen-induced congenital diaphragmatic hernia (CDH).

IF 1.5 3区 医学 Q2 PEDIATRICS
M Jank, M Kraljevic, A Ozturk Aptekmann, D Patel, M Boettcher, R LeDuc, R Keijzer
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引用次数: 0

Abstract

Purpose: Circular RNAs (circRNAs) are stable, non-coding RNAs with tissue- and developmental-specific expression making them suitable biomarkers for congenital anomalies. Current circRNA discovery pipelines have focused on human and mouse. We aim to bridge this gap by combining bioinformatics resources and used circtial1 as a model candidate in the nitrofen rat model of congenital diaphragmatic hernia (CDH).

Methods: Circtial1 backsplice junction sequences from a microarray were used to predict mature circRNA sequences and downstream pathways by miRNA interactions using CRAFT and circAtlas. We validated circtial1 expression using conventional PCR, amplicon sequencing, RT-Qpcr, and Basescope™ in situ hybridization.

Results: Expression of parental gene tial1 was decreased in nitrofen-induced lungs at embryonic day (E)15 (p = 0.004) and E21 (p = 0.008), while at E18, there was no significant difference (p = 0.65). At E21, circtial1 expression did not differ between CDH and control lungs (p = 0.07); however, there was a decreased expression in male pups (p = 0.0167). In situ hybridization confirmed low circtial1 expression. CircRNA::miRNA::mRNA interactions revealed pathway enrichment for inflammation/infection and neuron function/development.

Conclusion: For the first time, we report circRNA profiling in nitrofen-induced CDH with a sex-specific expression of circtial1. Current bioinformatics tools have significant challenges, but can guide hypothesis formation on their biological role.

cirtial1作为硝芬诱发的先天性膈疝(CDH)肺发育异常新标志物的验证和计算机功能预测。
目的:环状rna (circRNAs)是一种稳定的非编码rna,具有组织和发育特异性表达,使其成为先天性异常的合适生物标志物。目前circRNA的发现主要集中在人类和小鼠身上。我们的目标是通过结合生物信息学资源来弥补这一空白,并将circira1作为大鼠先天性膈疝(CDH)模型的候选模型。方法:利用微阵列中的circr1反向剪接连接序列,通过CRAFT和circAtlas的miRNA相互作用预测成熟的circRNA序列和下游途径。我们使用常规PCR、扩增子测序、RT-Qpcr和Basescope™原位杂交验证了ciral1的表达。结果:双亲基因tial1的表达在胚胎期(E)15 (p = 0.004)和E21 (p = 0.008)时降低,而在胚胎期(E) 18 (p = 0.65)时差异不显著。在E21时,CDH与对照肺间cirtir1表达无差异(p = 0.07);而雄性幼崽表达量明显降低(p = 0.0167)。原位杂交证实低circir1表达。CircRNA::miRNA::mRNA相互作用揭示了炎症/感染和神经元功能/发育的途径富集。结论:我们首次报道了氮肥诱导CDH中circRNA的性别特异性表达。目前的生物信息学工具面临着重大挑战,但可以指导关于其生物学作用的假设形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.00
自引率
5.60%
发文量
215
审稿时长
3-6 weeks
期刊介绍: Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children. The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include: -Review articles- Original articles- Technical innovations- Letters to the editor
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