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Updated: Jan 15, 2026
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
LINC00963 targeting miR-98-5p exacerbates sepsis-induced myocardial injury
Yanling Chen1, Xinming Li2, Xiemuziya Maimaitirexiati3
1Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Insights
LINC00963 upregulation worsens septic cardiomyopathy outcomes by downregulating miR-98-5p, increasing apoptosis and inflammation. Inhibiting LINC00963 protects heart cells, suggesting a therapeutic target for sepsis-induced heart damage.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- Septic cardiomyopathy (SCM) is a severe complication of sepsis with high mortality.
- The molecular mechanisms underlying SCM, particularly the role of long non-coding RNAs (lncRNAs), remain incompletely understood.
Purpose of the Study:
- To investigate the role and mechanism of lncRNA LINC00963 in the pathogenesis of septic cardiomyopathy.
- To explore the potential of targeting LINC00963 as a therapeutic strategy for SCM.
Main Methods:
- Patient cohort study (108 SCM patients, 85 controls) and in vitro/in vivo sepsis models (LPS stimulation, cecal ligation and puncture).
- Gene expression analysis (RT-qPCR), cell function assays (CCK8, flow cytometry), inflammatory marker detection (ELISA), and molecular interaction validation (dual luciferase reporter, RIP).
- Statistical analyses including Cox regression and Kaplan-Meier survival analysis.
Main Results:
- LINC00963 was significantly upregulated in SCM patients, septic mice, and LPS-treated cardiomyocytes, correlating with poorer survival rates.
- LINC00963 and BNP/NT-proBNP were independent predictors of mortality in SCM patients.
- LINC00963 knockdown reduced cardiomyocyte apoptosis and inflammation, while miR-98-5p inhibition reversed these effects, indicating LINC00963 targets miR-98-5p.
Conclusions:
- LINC00963 plays a detrimental role in septic cardiomyopathy by targeting and downregulating miR-98-5p, leading to increased apoptosis and inflammation.
- LINC00963 is a potential prognostic biomarker and therapeutic target for mitigating sepsis-induced cardiac injury.
Abstract:
The aim is to investigate the value and mechanism of action of LINC00963 in septic cardiomyopathy (SCM). A total of 85 patients with cardiomyopathy (control group) and 108 SCM patients were enrolled. An in vitro model was created by treating cardiomyocytes with 1 μg/mL of LPS. A sepsis mouse model was created using cecal ligation and puncture (CLP). Cox analysis was used to identify factors independently influencing mortality. Kaplan-Meier curves were used to record patient prognosis. RT-qPCR was used to detect gene expression. CCK8 and flow cytometry were employed to evaluate cell function. ELISA was used to detect inflammatory factor expression. Dual luciferase reporter and RIP validation were employed to confirm gene-targeted interactions. Upregulation of LINC00963 was observed in serum from patients with septic cardiomyopathy, heart tissue from septic mice, and LPS-infected cardiomyocytes, while miR-98-5p was downregulated. Patients with high LINC00963 expression had lower survival rates and were more likely to experience fatal outcomes. Both LINC00963 and BNP/NT-proBNP were both independent factors influencing patient mortality, and it was predicted that miR-98-5p was a target gene of LINC00963. Following si-LINC00963 transfection, apoptosis was reduced and inflammatory levels decreased in cardiomyocytes and myocardial tissue from sepsis-induced mice, and miR-98-5p was downregulated. However, the use of a miR-98-5p inhibitor reversed the cellular functional and inflammatory changes induced by LINC00963 knockdown. Knocking down LINC00963 reduces apoptosis and inflammation levels, and promotes cell proliferation by targeting miR-98-5p. This reduces the damage caused by sepsis to cardiomyocytes.
