当前位置:首页 / 基于GEO数据库联合分析高原病患者外周血差异表达miRNA及其上游转录因子和下游mRNA
论著.生物信息技术 | 更新时间:2024-05-09
|
基于GEO数据库联合分析高原病患者外周血差异表达miRNA及其上游转录因子和下游mRNA
Differentially expressed miRNAs in peripheral blood of patients with high altitude sickness and their upstream transcription factors and downstream mRNAs: a conjoint analysis based on the GEO database

广西医学 页码:284-291

作者机构:伊力亚斯·艾萨,博士,副教授,研究方向为疾病的药物干预及其分子机制。

基金信息:和田地区本级科技计划项目(202426);新疆维吾尔医学专科学校自然科学基金(SYS2024⁃002,2024ZR⁃004)

DOI:10.11675/j.issn.0253⁃4304.2024.02.18

  • 中文简介
  • 英文简介
  • 参考文献

目的 基于GEO数据库联合分析高原病患者外周血差异表达miRNA及其上游转录因子和下游mRNA,从而基于分子层面探讨高原病潜在的发病机制。方法 (1)在 GEO数据库获取与高原病相关的miRNA表达谱芯片(GSE90500数据集)和mRNA表达谱芯片(GSE29977数据集),再采用R语言3.6软件limma程序包筛选差异表达miRNA和差异表达mRNA。(2)利用FunRich软件预测差异表达miRNA的下游靶基因(mRNA)和上游转录因子,并对上游转录因子进行功能富集分析。使用R语言3.6软件、DAVID数据库对下游靶基因分别进行功能和通路富集分析。(3)对GSE29977数据集的差异表达mRNA与差异表达miRNA下游靶基因取交集,并根据miRNA及其靶基因的表达关系,筛选miRNA⁃mRNA调控轴。结果 (1)共筛选出14个差异表达miRNA及其385个下游靶基因、123个上游转录因子。差异表达miRNA主要富集的转录因子包括EGR1、RREB1、MYF5和MEF2A。(2)上游转录因子涉及的生物学过程主要包括信号转导、核酸代谢的调节、脂肪酸代谢、糖代谢、细胞因子和趋化因子介导的信号通路、细胞周期等。下游靶基因富集的生物学过程主要包括转录调控、心肌细胞增殖、血管生成和染色质重塑等,富集的信号通路主要包括PD⁃L1表达和PD⁃1免疫检查点通路、细胞衰老、MTOR信号通路、MAPK信号通路及PI3K/AKT信号通路等。(3)共筛选得到443个差异表达mRNA,与差异表达miRNA的下游靶基因取交集后获得与高原病相关的5个核心mRNA,并构建出hsa⁃miR⁃155⁃5p⁃MYO1D调控轴。结论 高原病中存在多个差异表达的miRNA,其上游转录因子EGR1、RREB1、MYF5、MEF2A可能是参与调控下游靶基因转录的核心因子;差异表达miRNA的上游转录因子和下游靶基因可能通过调控基因转录、细胞增殖与凋亡、炎症过程等生物学过程,共同参与高原病的发生、发展。hsa⁃miR⁃155⁃5p与下游靶基因MYO1D之间的调控关系可能在高原病的发生、发展中发挥重要的作用。

Objective To conjointly analyze the differentially expressed miRNAs in peripheral blood of patients with high altitude sickness and their upstream transcription factors and downstream mRNAs based on the GEO database, so as to explore potential pathogenesis of high altitude sickness based on molecular level. Methods (1) Expression profile chip of miRNAs (GSE90500 data set) and mRNAs expression profile chip (GSE29977 data set) related to high altitude sickness were obtained from the GEO database, and then the limma package of R language 3.6 software was used to screen differentially expressed miRNAs and mRNAs. (2) Downstream target genes (mRNAs) and upstream transcription factors of differentially expressed miRNAs were predicted by employing the FunRich software, and functional enrichment analysis was performed on upstream transcription factors. The R language 3.6 software, DAVID database were used to perform functional and pathway enrichment analyses on downstream target genes, respectively. (3) The intersection was obtained between differentially expressed mRNAs and downstream target genes of differentially expressed miRNAs in GSE29977 data set, and regulatory axis of miRNA⁃mRNA was screed according to the expression relation of miRNAs with its target genes. Results (1) A total of 14 differentially expressed miRNAs, and their 385 downstream target genes and 123 upstream transcription factors were screened. Differentially expressed miRNAs were mainly enriched in transcription factors, containing EGR1, RREB1, MYF5, and MEF2A. (2) Upstream transcription factors were mainly involved in biological processes of signal transduction, regulation of nucleic acid metabolism, fatty acid metabolism, glycometabolism, cytokine and chemokine mediated signaling pathways and cell cycle, etc. Downstream target genes were mainly enriched in biological processes in terms of transcriptional regulation, cardiomyocyte proliferation, angiogenesis, and chromatin remodeling, etc., and in signaling pathways with respect to PD⁃L1 expression and PD⁃1 immune checkpoint pathway, cell senescence, MTOR signaling pathway, MAPK signaling pathway, and PI3K/AKT signaling pathway, etc. (3) A total of 433 differentially expressed mRNAs were screened, and 5 core mRNAs related to high altitude sickness were obtained after acquiring the intersection with downstream target genes of differentially expressed miRNAs, as well as regulatory axis of hsa⁃miR⁃155⁃5p⁃MYO1D was established. Conclusion There are multiple differentially expressed miRNAs in high altitude sickness, their upstream transcription factors EGR1, RREB1, MYF5, and MEF2A may be the core factors involved in regulating downstream target genes transcription. Upstream transcription factors and downstream target genes of differentially expressed miRNAs may be jointly involved in the occurrence and development of high altitude sickness through regulating biological processes of gene transcription, cell proliferation and apoptosis, and inflammatory processes, etc. The regulatory relation between hsa⁃miR⁃155⁃5p and downstream target gene MYO1D may play an important role in the occurrence and development of high altitude sickness.

101

浏览量

15

下载量

0

CSCD

工具集