Transcriptome Sequencing Identifies Abnormal lncRNAs and mRNAs and Reveals Potentially Hub Immune-Related mRNA in Osteoporosis with Vertebral Fracture.

IF 3.5 3区 医学 Q2 GERIATRICS & GERONTOLOGY Clinical Interventions in Aging Pub Date : 2024-02-09 eCollection Date: 2024-01-01 DOI:10.2147/CIA.S441251
Rongxin Sun, Desheng Duan, Renzeng Li
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Abstract

Background: Recent studies have put forward the viewpoint of "bone immunology", which holds that the immune system and immune factors play an important regulatory role in the occurrence and development of osteoporosis. This study was intended to identify genetic characteristics of differentially expressed immune-related mRNA and lncRNA in patients combined with osteoporosis and vertebral fracture.

Methods: The peripheral blood samples were obtained from 3 groups of subjects: healthy control (HC), osteoporosis patients without vertebral fracture (OWF), and osteoporosis patients combined with vertebral fracture (OVF). The data were integrated to obtain differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs). Subsequently, the protein-protein interaction (PPI) networks were constructed. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Cytoscape-cytoHubba plug-in was used to identify key DEmRNAs. Furthermore, lncRNA-miRNA-mRNA, mRNA-lncRNA co-expression and transcription factors (TFs) networks were constructed. In addition, real-time PCR verification was performed.

Results: Totally of 3378 lncRNA-mRNA pairs were obtained, and the lncRNA co-expressed mRNA was mainly enriched in immune-related pathways, especially in GO-biological process (GO-BP) analysis. A total of 8 hub immune-related DEmRNAs were obtained, including IL18R1, IL18RAP, SLC11A1, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1. The TFs network showed that 8 hub immune-related DEmRNAs had interacting TFs. The co-expression network showed that 7 hub immune-related DEmRNAs (IL18R1, IL18RAP, SLC11A1, CSF2RA, IL-1R2, PGLYRP1, and IL1R1) had lncRNA-mRNA co-expression relationship. In addition, the lncRNA-miRNA-mRNA network includes 32 miRNAs, 7 hub immune-related mRNAs (IL18R1, IL18RAP, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1), and 11 lncRNAs.

Conclusion: Our study provides a novel and in-depth identification of co-expressed mRNAs and lncRNAs in patients combined with osteoporosis and vertebral fracture at a molecular level. This may provide new candidate biomarkers for the diagnosis of patients with high-risk fractures in the future.

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转录组测序鉴定异常 lncRNA 和 mRNA,揭示伴有椎体骨折的骨质疏松症中潜在的枢纽免疫相关 mRNA。
背景:近年来的研究提出了 "骨免疫学 "的观点,认为免疫系统和免疫因子在骨质疏松症的发生和发展中起着重要的调控作用。本研究旨在确定骨质疏松症合并椎体骨折患者免疫相关 mRNA 和 lncRNA 差异表达的遗传学特征:方法:采集健康对照组(HC)、未发生椎体骨折的骨质疏松症患者(OWF)和合并椎体骨折的骨质疏松症患者(OVF)3组受试者的外周血样本。对数据进行整合,得出差异表达的 mRNAs(DEmRNAs)和差异表达的 lncRNAs(DElncRNAs)。随后,构建了蛋白质-蛋白质相互作用(PPI)网络。进行了基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析。利用Cytoscape-cytoHubba插件鉴定了关键的DEmRNA。此外,还构建了lncRNA-miRNA-mRNA、mRNA-lncRNA共表达和转录因子(TFs)网络。此外,还进行了实时 PCR 验证:结果:共获得3378对lncRNA-mRNA,lncRNA共表达的mRNA主要富集于免疫相关通路,尤其是在GO-生物过程(GO-BP)分析中。共获得了8个与免疫相关的中枢DEmRNA,包括IL18R1、IL18RAP、SLC11A1、CSF2RA、CCR3、IL1R2、PGLYRP1和IL1R1。TFs网络显示,8个枢纽免疫相关DEmRNA有相互作用的TFs。共表达网络显示,7个中心免疫相关DEMRNA(IL18R1、IL18RAP、SLC11A1、CSF2RA、IL-1R2、PGLYRP1和IL1R1)存在lncRNA-mRNA共表达关系。此外,lncRNA-miRNA-mRNA网络包括32个miRNA、7个枢纽免疫相关mRNA(IL18R1、IL18RAP、CSF2RA、CCR3、IL1R2、PGLYRP1和IL1R1)和11个lncRNA:我们的研究在分子水平上对骨质疏松症合并椎体骨折患者中共同表达的 mRNA 和 lncRNA 进行了新颖而深入的鉴定。结论:我们的研究在分子水平上对合并骨质疏松症和椎体骨折患者中共同表达的 mRNA 和 lncRNA 进行了新颖而深入的鉴定,这可能为未来诊断高危骨折患者提供新的候选生物标志物。
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来源期刊
Clinical Interventions in Aging
Clinical Interventions in Aging GERIATRICS & GERONTOLOGY-
CiteScore
6.80
自引率
2.80%
发文量
193
审稿时长
6-12 weeks
期刊介绍: Clinical Interventions in Aging, is an online, peer reviewed, open access journal focusing on concise rapid reporting of original research and reviews in aging. Special attention will be given to papers reporting on actual or potential clinical applications leading to improved prevention or treatment of disease or a greater understanding of pathological processes that result from maladaptive changes in the body associated with aging. This journal is directed at a wide array of scientists, engineers, pharmacists, pharmacologists and clinical specialists wishing to maintain an up to date knowledge of this exciting and emerging field.
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