lncRNA MALAT1 Accelerates Skeletal Muscle Cell Apoptosis and Inflammatory Response in Sepsis by Decreasing BRCA1

Hui Yong1, Gangming Wu2, Jingyuan Chen2

  • 1Department of Anesthesiology, The First Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China.

Insights

Long non-coding RNA MALAT1 exacerbates sepsis by decreasing BRCA1 expression and increasing inflammation. Silencing MALAT1 reduced sepsis progression, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Sepsis is a life-threatening condition with high mortality.
  • Long non-coding RNAs (lncRNAs) play a role in inflammatory processes.
  • The role of lncRNA MALAT1 in sepsis development requires further investigation.

Purpose of the Study:

  • To investigate the role of lncRNA MALAT1 in sepsis.
  • To explore the mechanism by which MALAT1 influences sepsis progression.
  • To evaluate MALAT1 as a potential therapeutic target for sepsis.

Main Methods:

  • Established in vivo mouse and in vitro cell models of sepsis induced by lipopolysaccharide (LPS).
  • Measured expression levels of lncRNA MALAT1 and BRCA1 in septic models.
  • Manipulated MALAT1 expression to assess its effects on inflammatory factors, neutrophil migration, and skeletal muscle cell apoptosis.

Main Results:

  • High expression of lncRNA MALAT1 and low expression of BRCA1 were observed in sepsis.
  • MALAT1 regulates BRCA1 expression and nuclear export by recruiting EZH2.
  • Silencing MALAT1 reduced inflammatory cytokine levels (IL-6, IL-8, TNF-α), neutrophil migration, skeletal muscle cell apoptosis, and AKT-1 phosphorylation.

Conclusions:

  • lncRNA MALAT1 interacts with EZH2, promoting AKT-1 phosphorylation and decreasing BRCA1 expression.
  • This interaction aggravates sepsis progression.
  • lncRNA MALAT1 represents a promising therapeutic target for sepsis management.

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