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潜在的与缺氧相关的致病性基因 HK2 在新生儿坏死性小肠结肠炎(NEC)中的作用。

A potential pathogenic hypoxia-related gene HK2 in necrotizing enterocolitis (NEC) of newborns.

机构信息

Department of Neonatal, Children's Hospital Affiliated to Shandong University/Jinan Children's Hospital, No. 23976 Huaiyin District, Jinan, 250022, Shandong, People's Republic of China.

Department of Neonatal, LaoLing Maternity and Child Health Care Hospital, 118 Anju Road, Laoling County, Dezhou, Shandong Province, 253600, People's Republic of China.

出版信息

BMC Pediatr. 2022 Oct 26;22(1):617. doi: 10.1186/s12887-022-03664-w.

Abstract

BACKGROUND

Necrotizing enterocolitis (NEC) is a disastrous gastrointestinal disease of newborns, and the mortality rate of infants with NEC is approximately 20%-30%. The exploration of pathogenic targets of NEC will be conducive to timely diagnosis of NEC.

METHODS

The whole transcriptome RNA sequencing was performed on NEC samples to reveal the expression of lncRNAs, circRNAs, miRNAs and mRNAs. Using differential expression analysis, cross analysis, target prediction, enrichment analysis, the pathogenic ceRNA network and target was found.

RESULTS

Preliminarily, 281 DEmRNAs, 21 DEmiRNAs, 253 DElncRNAs and 207 DEcircRNAs were identified in NEC samples compared with controls. After target prediction and cross analyses, a key ceRNA regulatory network was built including 2 lncRNAs, 4 circRNAs, 2 miRNAs and 20 mRNAs. These 20 mRNAs were significantly enriched in many carbohydrate metabolism related pathways. After cross analysis of hypoxia-, carbohydrate metabolism-related genes, and 20 core genes, one gene HK2 was finally obtained. Dendritic cells activated were significantly differentially infiltrated and negatively correlated with HK2 expression in NEC samples.

CONCLUSIONS

The promising pathogenic hypoxia-related gene HK2 has been firstly identified in NEC, which might also involve in the carbohydrate metabolism in NEC.

摘要

背景

坏死性小肠结肠炎(NEC)是一种新生儿灾难性的胃肠道疾病,患 NEC 的婴儿死亡率约为 20%-30%。探索 NEC 的致病靶点将有助于及时诊断 NEC。

方法

对 NEC 样本进行全转录组 RNA 测序,以揭示 lncRNA、circRNA、miRNA 和 mRNA 的表达情况。采用差异表达分析、交叉分析、靶标预测、富集分析,发现致病 ceRNA 网络和靶标。

结果

与对照组相比,NEC 样本中初步鉴定出 281 个 DEmRNAs、21 个 DEmiRNAs、253 个 DElncRNAs 和 207 个 DEcircRNAs。经过靶标预测和交叉分析,构建了一个关键的 ceRNA 调控网络,包括 2 个 lncRNA、4 个 circRNA、2 个 miRNA 和 20 个 mRNA。这些 20 个 mRNA 显著富集在许多碳水化合物代谢相关途径中。在缺氧、碳水化合物代谢相关基因和 20 个核心基因的交叉分析后,最终获得了一个基因 HK2。在 NEC 样本中,激活的树突状细胞明显不同程度地浸润,并且与 HK2 表达呈负相关。

结论

首次在 NEC 中发现有前景的致病相关基因 HK2,其可能也参与 NEC 中的碳水化合物代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7586/9597967/fbe9e8d5eb0e/12887_2022_3664_Fig1_HTML.jpg

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