LncRNA HOTAIR Promotes LPS-Induced Inflammation and Apoptosis of Cardiomyocytes via Lin28-Mediated PDCD4 Stability

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Sepsis Pathophysiology

Background:

• Sepsis is a leading cause of intensive care unit mortality.
• Septic cardiomyopathy is a significant complication of sepsis.
• The precise molecular mechanisms of long non-coding RNA HOTAIR in septic cardiomyopathy remain unclear.

Purpose of the Study:

• To elucidate the role and mechanism of long non-coding RNA HOTAIR in lipopolysaccharide (LPS)-induced septic cardiomyopathy.
• To investigate the interaction between HOTAIR, Lin28, and PDCD4 in the context of sepsis.

Main Methods:

• In vitro studies using H9C2 cells treated with LPS and transfected with HOTAIR or PDCD4 related constructs.
• Quantitative reverse transcription PCR (qRT-PCR) to measure gene and cytokine levels.
• Flow cytometry for apoptosis detection.
• RNA pull-down and RIP assays to confirm molecular interactions.
• In vivo studies in mice with LPS-induced septic cardiomyopathy using AAV9-sh-HOTAIR.
• ELISA for inflammatory cytokines (TNF-α, IL-6, IL-1β).
• Western blot for protein expression (LIN28, PDCD4).
• Echocardiography for cardiac function assessment.

Main Results:

• Knockdown of HOTAIR significantly inhibited LPS-induced inflammation and apoptosis in H9C2 cells.
• HOTAIR was found to enhance PDCD4 stability, thereby promoting inflammatory response and apoptosis.
• Lin28, an RNA-binding protein, interacts with both HOTAIR and PDCD4.
• In vivo experiments confirmed that HOTAIR knockdown ameliorated cardiac dysfunction and reduced inflammatory factor secretion in septic mice.

Conclusions:

• The HOTAIR/Lin28/PDCD4 axis is a critical regulator in sepsis-induced cardiomyopathy.
• HOTAIR promotes sepsis by stabilizing PDCD4, leading to inflammation and apoptosis.
• This axis presents a potential therapeutic target for sepsis treatment.