Genome-wide identification and functional analysis of dysregulated alternative splicing profiles in sepsis

Journal of Inflammation

Brief Report

Reyila Tuerhong¹  Jinliang Jiao¹  Baihetinisha Tuerdi¹  Mengchen Li¹  Gulisitan Aili¹  Dilixiati Tuerdimaimaiti¹  Ajiguli Kulaxi¹  Shaotao Kang¹  Wolazihan Madeniyati¹  Buzukela Abuduaini² 

[1]Department of RICU, The First Affiliated Hospital of Xinjiang Medical University, 393 South Li Yu Shan Road, 830054, Wulumuqi, Xinjiang, China

[2]The Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, 830054, Wulumuqi, Xinjiang, China

关键词: Alternative splicing;    Sepsis;    Apoptosis;    RBP;    Immune effector cells;   

DOI  :  10.1186/s12950-023-00355-w

 received in 2022-12-29, accepted in 2023-08-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAn increasing body of evidence now shows that the long-term mortality of patients with sepsis are associated with various sepsis-related immune cell defects. Alternative splicing (AS), as a sepsis-related immune cell defect, is considered as a potential immunomodulatory therapy target to improve patient outcomes. However, our understanding of the role AS plays in sepsis is currently insufficient.AimThis study investigated possible associations between AS and the gene regulatory networks affecting immune cells. We also investigated apoptosis and AS functionality in sepsis pathophysiology.MethodsIn this study, we assessed publicly available mRNA-seq data that was obtained from the NCBI GEO dataset (GSE154918), which included a healthy group (HLTY), a mild infection group (INF1), asepsis group (Seps), and a septic shock group (Shock). A total of 79 samples (excluding significant outliers) were identified by a poly-A capture method to generate RNA-seq data. The variable splicing events and highly correlated RNA binding protein (RBP) genes in each group were then systematically analyzed.ResultsFor the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p <= 0.01) across the four groups. In the sepsis group, the genes related to significant AS events, such as, SHISA5 and IFI27, were mostly enriched in the cell apoptosis pathway. Furthermore, we identified differential splicing patterns within each of the four groups. Significant differences in the expression of RNA Binding Protein(RBP) genes were observed between the control group and the sepsis group. RBP gene expression was highly correlated with variant splicing events in sepsis, as determined by co-expression analysis; The expression of DDX24, CBFA2T2, NOP, ILF3, DNMT1, FTO, PPRC1, NOLC1 RBPs were significant reduced in sepsis compared to the healthy group. Finally, we constructed an RBP-AS functional network.ConclusionAnalysis indicated that the RBP-AS functional network serves as a critical post-transcriptional mechanism that regulates the development of sepsis. AS dysregulation is associated with alterations in the regulatory gene expression network that is involved in sepsis. Therefore, the RBP-AS expression network could be useful in refining biomarker predictions in the development of new therapeutic targets for the pathogenesis of sepsis.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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