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急性呼吸窘迫综合征新生儿环状RNA差异表达的芯片及生物信息学分析

Microarray and Bioinformatics Analysis of Circular RNA Differential Expression in Newborns With Acute Respiratory Distress Syndrome.

作者信息

Zhou Huan, Chanda Bwalya, Chen Yu-Fei, Wang Xue-Juan, You Ming-Yu, Zhang Yi-Han, Cheng Rui, Yang Yang, Chen Xiao-Qing

机构信息

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Front Pediatr. 2021 Nov 2;9:728462. doi: 10.3389/fped.2021.728462. eCollection 2021.

Abstract

Previous studies pointed out that a variety of microRNAs (miRNAs) are involved in the pathogenesis of neonatal acute respiratory distress syndrome (NARDS) and play different roles in the pathological process. However, there have been few studies reporting the connection between circular RNA (circRNA) and NARDS, so the expression profile of circRNAs in newborns with acute respiratory distress syndrome remains largely unknown. In the present study, 10 samples obtained from remaining clinical blood samples of newborns hospitalized in a neonatal ward of the First Affiliated Hospital of Nanjing Medical University from January 2020 to October 2020 were divided into the "NARDS" group and "non-NARDS" group according to the Montelux standard and then were analyzed in microarray, and 10 other samples collected from the same place and from January 1, 2021 to August 31, 2021, were used to do RT-qPCR experiment. circRNA expression profiles, in which 741 circRNAs were downregulated and 588 were upregulated, were screened with circRNA high-throughput sequencing. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of parent genes of the differentially expressed circRNAs revealed that these circRNAs may be related to the process of protein synthesis and metabolism in NARDS. Moreover, five circRNAs-hsa_circ_0058495, hsa_circ_0000367, hsa_circ_0005389, hsa_circ_0059571, and hsa_circ_0006608-were selected randomly among the top 10 circRNAs of the downregulated or upregulated expression profiles. Then, bioinformatics tools were used to predict correlative miRNA and its target genes, which were also subjected to the same bioinformatics analysis for further study. The top 30 enriched KEGG pathway analyses of the 125 target genes suggested that these target genes are widely involved in the synthesis and secretion of endocrine hormones, and the top 30 enriched GO terms based on the 125 target genes are also focused on the protein and DNA processing. Thus, the present results show that circRNAs could promote the inflammation of NARDS which may provide a new therapeutic direction and it can be used as molecular markers for early diagnosis of NARDS, but further molecular biology verification is needed to define the specific role of differentially expressed circRNAs in NARDS.

摘要

以往研究指出,多种微小RNA(miRNA)参与新生儿急性呼吸窘迫综合征(NARDS)的发病机制,并在病理过程中发挥不同作用。然而,关于环状RNA(circRNA)与NARDS之间联系的研究较少,因此急性呼吸窘迫综合征新生儿中circRNA的表达谱仍 largely未知。在本研究中,将2020年1月至2020年10月在南京医科大学第一附属医院新生儿病房住院的新生儿剩余临床血样中获取的10份样本,根据蒙特勒克斯标准分为“NARDS”组和“非NARDS”组,然后进行芯片分析,另外从同一地点收集的、2021年1月1日至2021年8月31日的10份样本用于进行RT-qPCR实验。通过circRNA高通量测序筛选出circRNA表达谱,其中741种circRNA下调,588种上调。随后,对差异表达circRNA的亲本基因进行基因本体论和京都基因与基因组百科全书分析,结果显示这些circRNA可能与NARDS中的蛋白质合成和代谢过程有关。此外,在下调或上调表达谱的前10种circRNA中随机选择了5种circRNA——hsa_circ_0058495、hsa_circ_0000367、hsa_circ_0005389、hsa_circ_0059571和hsa_circ_0006608。然后,使用生物信息学工具预测相关miRNA及其靶基因,并对其进行相同的生物信息学分析以作进一步研究。对125个靶基因进行的前30个富集KEGG通路分析表明,这些靶基因广泛参与内分泌激素的合成和分泌,基于125个靶基因的前30个富集GO术语也集中在蛋白质和DNA加工方面。因此,本研究结果表明circRNA可能促进NARDS的炎症反应,这可能为其提供新的治疗方向,并且可作为NARDS早期诊断的分子标志物,但需要进一步的分子生物学验证来确定差异表达circRNA在NARDS中的具体作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f607/8592891/4aa752b542c8/fped-09-728462-g0001.jpg

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