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基于生物信息学的腹主动脉瘤免疫微环境中核心铜死亡相关生物标志物的鉴定。

Identification of core cuprotosis-correlated biomarkers in abdominal aortic aneurysm immune microenvironment based on bioinformatics.

机构信息

Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Vascular Centre of Shanghai Jiao Tong University, Shanghai, China.

出版信息

Front Immunol. 2023 Apr 17;14:1138126. doi: 10.3389/fimmu.2023.1138126. eCollection 2023.

Abstract

BACKGROUND

The occurrence of abdominal aortic aneurysms (AAAs) is related to the disorder of immune microenvironment. Cuprotosis was reported to influence the immune microenvironment. The objective of this study is to identify cuprotosis-related genes involved in the pathogenesis and progression of AAA.

METHODS

Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in mouse were identified following AAA through high-throughput RNA sequencing. The enrichment analyses of pathway were selected through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The validation of cuprotosis-related genes was conducted through immunofluorescence and western blot analyses.

RESULTS

Totally, 27616 lncRNAs and 2189 mRNAs were observed to be differentially expressed (|Fold Change| ≥ 2 and q< 0.05) after AAA, including 10424 up-regulated and 17192 down-regulated lncRNAs, 1904 up-regulated and 285 down-regulated mRNAs. Gene ontology and KEGG pathway analysis showed that the DElncRNAs and DEmRNAs were implicated in many different biological processes and pathways. Furthermore, Cuprotosis-related genes (NLRP3, FDX1) were upregulated in the AAA samples compared with the normal one.

CONCLUSION

Cuprotosis-related genes (NLRP3,FDX1) involved in AAA immune environment might be critical for providing new insight into identification of potential targets for AAA therapy.

摘要

背景

腹主动脉瘤(AAA)的发生与免疫微环境紊乱有关。铜死亡被报道影响免疫微环境。本研究旨在鉴定与 AAA 发病机制和进展相关的铜死亡相关基因。

方法

通过高通量 RNA 测序鉴定 AAA 后小鼠差异表达的长链非编码 RNA(lncRNA)和信使 RNA(mRNA)。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)选择途径的富集分析。通过免疫荧光和 Western blot 分析验证铜死亡相关基因。

结果

AAA 后观察到 27616 个 lncRNA 和 2189 个 mRNA 表达差异(|Fold Change|≥2,q<0.05),包括 10424 个上调和 17192 个下调的 lncRNA,1904 个上调和 285 个下调的 mRNA。GO 和 KEGG 通路分析表明,差异表达的 lncRNA 和 mRNA 参与了许多不同的生物学过程和通路。此外,与正常样本相比,AAA 样本中铜死亡相关基因(NLRP3、FDX1)上调。

结论

参与 AAA 免疫环境的铜死亡相关基因(NLRP3、FDX1)可能为鉴定 AAA 治疗的潜在靶点提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a131/10150024/ed2e35b323c7/fimmu-14-1138126-g001.jpg

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