Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction

Cardiovasc Toxicol. 2024 Oct;24(10):1125-1138. doi: 10.1007/s12012-024-09903-z. Epub 2024 Jul 31.

Abstract

The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.

Keywords: Diagnosis; Inflammation; MCM3AP-AS1; SIMD; Sepsis.

MeSH terms

  • Acetyltransferases
  • Aged
  • Apoptosis*
  • Biomarkers / blood
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism
  • Case-Control Studies
  • Cell Line
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • Predictive Value of Tests
  • RNA, Long Noncoding* / blood
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sepsis* / complications
  • Sepsis* / diagnosis
  • Signal Transduction

Substances

  • Acetyltransferases
  • Biomarkers
  • Intracellular Signaling Peptides and Proteins
  • MCM3AP protein, human
  • MicroRNAs
  • RNA, Long Noncoding