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Updated: Nov 5, 2025
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Published on: June 15, 2018
MiR-210-3p Enhances Cardiomyocyte Apoptosis and Mitochondrial Dysfunction by Targeting the NDUFA4 Gene in
Dandan Chen1, Yu Hou1, Xingjun Cai2
1Department of Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University.
Abstract:
Sepsis-induced myocardial dysfunction (SIMD) is a common complication with high incidence rates in sepsis patients. This study aimed to investigate the roles of miR-210-3p in regulating cardiomyocyte apoptosis and mitochondrial dysfunction associated with SIMD pathogenesis.A rat sepsis model was established by cecal ligation and puncture. Serum inflammatory factors, myocardial tissue apoptosis, and expression of miR-210-3p were evaluated. In vitro, miR-210-3p expression in H9C2 cells was altered by transfection with its mimics or inhibitors. H9C2 viability was assessed via CCK-8 assay, and reactive oxygen species (ROS) production and apoptosis were detected through flow cytometry. The targeting regulatory relations between miR-210-3p and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4) were validated by dual luciferase reporter assay.The rat sepsis model showed increased serum TNF-α and IL-6 levels, significant myocardial tissue injuries and apoptosis with decreased Bcl-2 and increased Caspase-1 protein levels. In vitro, septic rat serum suppressed viability, promoted ROS production and apoptosis, impaired COX IV activities and increased cytochrome release in H9C2 cells. The expression of miR-210-3p was greatly increased in myocardial tissues of septic rats and septic serum-treated H9C2 cells. miR-210-3p directly binds to the 3' UTR of the NDUFA4 gene. Septic rat serum suppressed NDUFA4 and Iron-Sulfur Cluster Assembly Protein U gene expressions in H9C2 cells. The above cellular and molecular alterations in H9C2 cells induced by septic serum were enhanced by miR-210-3p mimics and abrogated by miR-210-3p inhibitors.miR-210-3p promoted SIMD pathogenesis by targeting NDUFA4 to enhance cardiomyocyte apoptosis and impair mitochondrial function.
Insights
MicroRNA-210-3p exacerbates sepsis-induced myocardial dysfunction by promoting cardiomyocyte apoptosis and mitochondrial damage. Targeting this microRNA may offer a therapeutic strategy for sepsis patients.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Sepsis-induced myocardial dysfunction (SIMD) is a critical complication in sepsis patients.
- Understanding the molecular mechanisms underlying SIMD is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-210-3p (miR-210-3p) in regulating cardiomyocyte apoptosis and mitochondrial dysfunction in SIMD.
- To elucidate the molecular targets and pathways affected by miR-210-3p in SIMD pathogenesis.
Main Methods:
- Established a rat sepsis model using cecal ligation and puncture.
- Assessed serum inflammatory factors, myocardial apoptosis, and miR-210-3p expression.
- Utilized in vitro cell culture (H9C2 cells) with miR-210-3p mimics/inhibitors to evaluate cell viability, reactive oxygen species (ROS) production, and apoptosis.
- Validated the direct binding of miR-210-3p to NDUFA4 using a dual luciferase reporter assay.
Main Results:
- Septic rats exhibited elevated inflammatory markers (TNF-α, IL-6), myocardial injury, apoptosis, and altered Bcl-2/Caspase-1 levels.
- Septic serum impaired H9C2 cell viability, increased ROS, and induced apoptosis.
- miR-210-3p expression was significantly upregulated in septic myocardial tissues and H9C2 cells.
- miR-210-3p directly targets NDUFA4, and its upregulation exacerbates SIMD-related cellular and mitochondrial dysfunction.
Conclusions:
- miR-210-3p plays a pro-apoptotic and pro-dysfunction role in sepsis-induced myocardial dysfunction.
- Targeting miR-210-3p may represent a novel therapeutic approach for managing SIMD.
