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J Pediatr Infect Dis 2024; 19(01): 039-051
DOI: 10.1055/s-0043-1777093
Original Article

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Yue Li
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Zhongqiang Liu
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Ruixiang Tang
2   Key Laboratory of Bioresources and Eco-Environment (MOE), College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Maoyun Deng
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Jinlin Wu
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Guoyan Lu
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Yifei Li 
1   Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
,
Zhenxin Fan
2   Key Laboratory of Bioresources and Eco-Environment (MOE), College of Life Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China
› Author Affiliations Funding This work was supported by grants from the Technology Project of Sichuan Province of China (2021YFQ0061) and the National Natural Science Foundation of China (82270249). The funding did not participate in the design of the study and collection, analysis, and interpretation of data or in writing the manuscript.
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Abstract

Objective Long noncoding RNAs (lncRNAs) have been implicated in various biological processes, particularly in the regulation of inflammatory responses and myocardial injuries. Notably, the role of lncRNAs in sepsis-induced cardiomyopathy (SIC) has been highlighted. However, a comprehensive analysis investigating the specific circulating lncRNAs associated with SIC has yet to be conducted. Therefore, we conducted a study involving samples from healthy controls, sepsis patients without myocardial injuries, individuals with cardiac dysfunction following heart surgery, and those with SIC, aiming to identify the distinct lncRNAs involved in SIC.

Methods A total of 12 blood samples were collected, including healthy controls, sepsis patients without myocardial injuries, patients with cardiac surgery-related myocardial injuries, and patients with SIC, who were aged from 10 to 22 months. Transcriptome sequencing was conducted to identify differentially expressed (DE) lncRNAs and mRNAs. Venn plots were employed to identify the DE RNAs specific to SIC. Subsequently, enrichment analyses were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms. A coexpression network between lncRNAs and mRNAs was constructed, focusing on protein–protein interaction features. Then, further validation had been done in a consecutive larger cohort.

Results We identified independent DE mRNAs and lncRNAs specific to SIC patients. The analysis of DE mRNAs revealed that immune activation, particularly innate immune activity, was the primary distinction between sepsis with or without myocardial injuries. Furthermore, cytokine production, particularly interleukin-1 secretion, played a significant role in inducing SIC. The expression profiles of DE lncRNAs showed considerable enrichment in shared topics with mRNAs. Subsequently, we identified lncRNAs targeting the DE mRNAs, many of which were involved in immune responses and cytokine production. We established a coexpression network between lncRNAs and mRNAs, leading to the discovery of a novel lncRNA (TCONS_00136255). Finally, we successfully validated TCONS_00136255, demonstrating its acceptable diagnostic accuracy and its role in regulating major molecular processes involved in SIC.

Conclusion lncRNAs actively participate in the significant biological changes associated with immune responses in sepsis-induced myocardial injuries. These lncRNAs interact with mRNAs to modulate inflammation activity and cytokine production. Notably, the identification of the novel lncRNA (TCONS_00136255) highlights its crucial regulatory role in SIC.

Keywords

lncRNA - sepsis - cardiomyopathy - myocardial injuries - TCONS_00136255

Ethical Approval and Consent to Participate

This study was approved by the Ethics Committee of West China Second Hospital of Sichuan University (2014034). Informed consent from all the patient's parents was obtained, including the patient's clinical and imaging details in the manuscript for the purpose of publication.


Consent for Publication

Not Applicable.


Availability of Data and Material

All the data are presented in the manuscript. Other datasets used in this study are available from the corresponding author upon reasonable request.


Authors' Contributions

Y.L., Z.L., R.T., M.D., J.W., G.L., and Y.L. collected the clinical data. Y.L. and Y.L. reviewed the literature and contributed to manuscript drafting; R.T. and Z.F. performed the sequencing analysis. Y.L. and G.L. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. Y.L. and Z.F. were responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.




Publication History

Received: 12 June 2023

Accepted: 17 October 2023

Article published online:
11 December 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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