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通过综合生物信息学方法鉴定与缺血性中风相关的差异表达微小RNA

Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches.

作者信息

Jiang Shengqiang, Wu Jie, Geng Yan, Zhang Yuting, Wang Yupeng, Wu Jinrong, Lu Chunqu, Luo Guoxuan, Zan Jie, Zhang Yong

机构信息

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

Department of Neurosurgery, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, China.

出版信息

Int J Genomics. 2022 Oct 10;2022:9264555. doi: 10.1155/2022/9264555. eCollection 2022.

Abstract

Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. This study aims to find the crucial exosomal miRNAs associated with IS by using bioinformatics methods, reveal potential biomarkers for IS, and investigate the association between the identified biomarker and immune cell pattern in the peripheral blood of IS patients. In this study, 3 up-regulated miRNAs (hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p) miRNAs in the serum exosomes between IS patients and healthy controls from GEO database (GSE199942) and 25 down-regulated genes of peripheral blood mononuclear cells of IS patients from GSE22255 were obtained with the help of the R software. GO annotation and KEGG pathway enrichment analysis showed that the 25 down-regulated genes were associated with coenzyme metabolic process and were mainly enriched in the N-glycan biosynthesis pathway. Furthermore, we performed the LASSO algorithm to narrow down the above 25 intersected genes, and identified 8 key genes which had a good diagnostic value in discriminating IS patients from the healthy controls analyzed with ROC curve. CIBERSORT algorithm indicated that the abundance of M0 macrophages and resting mast cells was significantly lower than that of the control group. The spearman correlation analysis showed that STT3A was negatively correlated with the proportion of follicular helper T cells, activated NK cells and resting dendritic cells. Finally, GSE117064 showed that has-miR-16-5p was more advantageous for diagnosing stroke. In conclusion, hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p are identified as specific related exosomal miRNAs for IS patients. These genes may provide new targets for the early identification of IS.

摘要

缺血性中风(IS)是全球致残和致死的主要原因之一。本研究旨在通过生物信息学方法寻找与IS相关的关键外泌体微小RNA(miRNA),揭示IS的潜在生物标志物,并研究已鉴定的生物标志物与IS患者外周血免疫细胞模式之间的关联。在本研究中,借助R软件从GEO数据库(GSE199942)中获取了IS患者与健康对照血清外泌体中3个上调的miRNA(hsa-miR-15b-5p、hsa-miR-184和hsa-miR-16-5p),并从GSE22255中获取了IS患者外周血单个核细胞的25个下调基因。基因本体(GO)注释和京都基因与基因组百科全书(KEGG)通路富集分析表明,这25个下调基因与辅酶代谢过程相关,主要富集于N-聚糖生物合成通路。此外,我们进行了套索(LASSO)算法以缩小上述25个交集基因范围,并鉴定出8个关键基因,这些基因在用ROC曲线分析区分IS患者与健康对照时具有良好的诊断价值。CIBERSORT算法表明,M0巨噬细胞和静息肥大细胞的丰度显著低于对照组。Spearman相关性分析表明,STT3A与滤泡辅助性T细胞、活化自然杀伤细胞和静息树突状细胞的比例呈负相关。最后,GSE117064表明has-miR-16-5p对中风诊断更具优势。总之,hsa-miR-15b-5p、hsa-miR-184和hsa-miR-16-5p被鉴定为IS患者特异性相关的外泌体miRNA。这些基因可能为IS的早期识别提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a093/9576445/e97d5ad45f98/IJG2022-9264555.001.jpg

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