Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 3: 282 - 291

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.03.004

Basic research

Identification of prognostic long non-coding RNA and construction of competing endogenous RNA networks in pediatric sepsis

  • LIU Tiantian ,
  • ZHAO Yilin ,
  • NING Jingjing ,
  • ZHANG Yucai ,
  • WANG Chunxia
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  • 1.Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China
    2.Laboratory of Critical Care Translational Medicine, Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China
WANG Chunxia, E-mail: karencx0465@163.com.

Received date: 2024-05-06

  Accepted date: 2024-12-26

  Online published: 2025-03-28

Supported by

National Natural Science Foundation of China(82171729);Shanghai Natural Science Foundation(23ZR1453000);“Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20171928)

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Abstract

Objective ·To screen a long non-coding RNA (lncRNA) signature and construct a competing endogenous RNA (ceRNA) network associated with the prognosis of pediatric sepsis based on the Gene Expression Omnibus (GEO) database, and explore their potential application value in the prognosis assessment of children with sepsis. Methods ·Microarray data in GSE4607, GSE26440, GSE26378, and GSE9692 in the GEO database were used to compare the differences in lncRNA profiles between the survival and non-survival groups of children with septic shock. Then, multivariate linear regression, LASSO analysis, and receiver operating characteristic (ROC) curves were used to evaluate the capacity of the lncRNA signature for predicting the outcome of pediatric sepsis. The potential targeted microRNAs (miRNAs) and their downstream mRNAs, targeted by the screened lncRNAs, were used to construct a protein-protein interaction (PPI) network and perform pathway enrichment analysis. Results ·Transcriptomic data from GSE4607, GSE26440, GSE26378 and GSE9692 revealed 55 differentially expressed lncRNAs associated with prognosis, and miR503 host gene (MIR503HG), TAPT1 antisense RNA 1 (TAPT1-AS1), apoptosis-associated transcript in bladder cancer (AATBC), SBF2 antisense RNA 1 (SBF2-AS1), MGC16275, and small nucleolar RNA host gene 15 (SNHG15) were identified as a 6-lncRNA signature (lncSig6) associated with the prognosis of pediatric septic shock by LASSO regression analysis. The area under the ROC curve (AUC) of lncSig6 was 0.859 (95% CI 0.722‒0.996) and 0.854 (95% CI 0.687‒1.000) in internal and external validation, respectively. As lncRNA act as miRNA sponge, a lncRNA-miRNA-mRNA network based on 3 lncRNAs (MIR503HG, SNHG15, and SBF2-AS1) was constructed and involved in the regulation of signaling pathways, including forkhead box O (FoxO) signaling pathway, phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signaling pathway, cell senescence, insulin signaling pathway, hypoxia-inducible protein-1 (HIF-1) signaling pathway and advanced glycation end products (AGEs) and receptor of AGEs (RAGE) signaling pathway. Conclusion ·The lncSig6 can be used as an evaluation method to predict the prognosis of septic shock in children, and the constructed ceRNA molecular networks can provide an experimental basis for the study of signaling pathways.

Key words： pediatric sepsis; long non-coding RNA; competing endogenous RNA; prognostic biomarker

Cite this article

LIU Tiantian , ZHAO Yilin , NING Jingjing , ZHANG Yucai , WANG Chunxia . Identification of prognostic long non-coding RNA and construction of competing endogenous RNA networks in pediatric sepsis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(3) : 282 -291 . DOI: 10.3969/j.issn.1674-8115.2025.03.004

References

1 RUDD K E, JOHNSON S C, AGESA K M, et al. Global, regional, and national sepsis incidence and mortality, 1990—2017: analysis for the Global Burden of Disease Study[J]. Lancet, 2020, 395(10219): 200-211.
2 BASSAT Q, BLAU D M, OGBUANU I U, et al. Causes of death among infants and children in the child health and mortality prevention surveillance (CHAMPS) network[J]. JAMA Netw Open, 2023, 6(7): e2322494.
3 SCHLAPBACH L J, SCOTT WATSON R, SORCE L R, et al. International consensus criteria for pediatric sepsis and septic shock[J]. JAMA, 2024, 331(8): 665-674.
4 NELSON SANCHEZ-PINTO L, BENNETT T D, DEWITT P E, et al. Development and validation of the Phoenix criteria for pediatric sepsis and septic shock[J]. JAMA, 2024, 331(8): 675-686.
5 WEN R, ZHANG T N, ZHANG T, et al. A novel long noncoding RNA-lncRNA-AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide-induced myocardial depression[J]. FASEB J, 2023, 37(8): e23063.
6 BAI J Q, CHEN S Y. lncRNA CASC9 enhances the stability of SOCS-1 by combining with FUS to alleviate sepsis-induced liver injury[J]. Cytokine, 2023, 171: 156346.
7 MIAO R F, TU J. lncRNA CDKN2B-AS1 interacts with LIN28B to exacerbate sepsis-induced acute lung injury by inducing HIF-1α/NLRP3-mediated pyroptosis[J]. Kaohsiung J Med Sci, 2023, 39(9): 883-895.
8 LU Z L, YU H Y, XU Y F, et al. LNCZNF33B-2:1 gene rs579501 polymorphism is associated with organ dysfunction and death risk in pediatric sepsis[J]. Front Genet, 2022, 13: 947317.
9 LIAO Y, WANG R, WEN F Q. Diagnostic and prognostic value of long noncoding RNAs in sepsis: a systematic review and meta-analysis[J]. Expert Rev Mol Diagn, 2022, 22(8): 821-831.
10 NIE X B, DENG W, ZHOU H, et al. Long noncoding RNA MCM3AP-AS1 attenuates sepsis-induced cardiomyopathy by improving inflammation, oxidative stress, and mitochondrial function through mediating the miR-501-3p/CADM1/STAT3 axis[J]. Int Immunopharmacol, 2024, 128: 111500.
11 YANG N, YAN N, BAI Z H, et al. FTO attenuates LPS-induced acute kidney injury by inhibiting autophagy via regulating SNHG14/miR-373-3p/ATG7 axis[J]. Int Immunopharmacol, 2024, 128: 111483.
12 SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8): 801-810.
13 ZHANG Q, WANG C L, LI S L, et al. Screening of core genes prognostic for sepsis and construction of a ceRNA regulatory network[J]. BMC Med Genomics, 2023, 16(1): 37.
14 DING X, LIANG W Q, XIA H J, et al. Analysis of immune and prognostic-related lncRNA PRKCQ-AS1 for predicting prognosis and regulating effect in sepsis[J]. J Inflamm Res, 2024, 17: 279-299.
15 CHEN J S, TANG S, KE S, et al. Ablation of long noncoding RNA MALAT1 activates antioxidant pathway and alleviates sepsis in mice[J]. Redox Biol, 2022, 54: 102377.
16 SHI C C, ZHAO Y Q, LI Q, et al. lncRNA SNHG14 plays a role in sepsis-induced acute kidney injury by regulating miR-93[J]. Mediators Inflamm, 2021, 2021: 5318369.
17 LIN H, WANG J G, WANG T, et al. The lncRNA MIR503HG/miR-224-5p/TUSC3 signaling cascade suppresses gastric cancer development via modulating ATF6 branch of unfolded protein response[J]. Front Oncol, 2021, 11: 708501.
18 WANG T W, LIANG D, YANG H Y. SNHG15 facilitated malignant behaviors of oral squamous cell carcinoma through targeting miR-188-5p/DAAM1[J]. J Oral Pathol Med, 2021, 50(7): 681-691.
19 CHEN Q, GUO S M, HUANG H Q, et al. Long noncoding RNA SBF2-AS1 contributes to the growth and metastatic phenotypes of NSCLC via regulating miR-338-3p/ADAM17 axis[J]. Aging (Albany NY), 2020, 12(18): 17902-17920.
20 TIAN Y, LI X X, BAI C, et al. lncRNA MIR503HG targets miR-191-5p/PLCD1 axis and negatively modulates apoptosis, extracellular matrix disruption, and inflammation in abdominal aortic aneurysm[J]. Mediators Inflamm, 2023, 2023: 4003618.
21 YU Y H, CAI Y P, ZHOU H. lncRNA SNHG15 regulates autophagy and prevents cerebral ischaemia-reperfusion injury through mediating miR-153-3p/ATG5 axis[J]. J Cell Mol Med, 2024, 28(5): e17956.
22 ZHANG L, LI B, LI W, et al. miR-107 attenuates sepsis-induced myocardial injury by targeting PTEN and activating the PI3K/AKT signaling pathway[J]. Cells Tissues Organs, 2023, 212(6): 523-534.
23 ZHU W L, HUANG X P, QIU S, et al. miR-142-5p encapsulated by serum-derived extracellular vesicles protects against acute lung injury in septic rats following remote ischemic preconditioning via the PTEN/PI3K/Akt axis[J]. J Innate Immun, 2022, 14(5): 532-542.
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