LncRNA Tincr regulates PKCɛ expression in a miR-31-5p-dependent manner in cardiomyocyte hypertrophy

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Genetics

Background:

• Cardiomyocyte hypertrophy is a key driver of heart failure and mortality.
• The precise molecular mechanisms underlying cardiomyocyte hypertrophy remain incompletely understood.
• Long non-coding RNAs (lncRNAs) are emerging as critical regulators in cardiovascular diseases.

Purpose of the Study:

• To elucidate the role of lncRNA Tincr in the pathogenesis of cardiomyocyte hypertrophy.
• To identify the molecular targets and regulatory pathways of Tincr in cardiac cells.
• To explore the potential of the Tincr-miR-31-5p-PRKCE axis as a therapeutic strategy for heart disease.

Main Methods:

• Utilized transverse aortic constriction (TAC) mouse models and H9C2 cell lines to study cardiomyocyte hypertrophy.
• Quantified lncRNA Tincr expression levels via real-time PCR.
• Employed bioinformatics analysis (StarBase), dual-luciferase reporter assays, and western blotting to validate molecular interactions.
• Performed gene knockdown and overexpression experiments to assess functional effects.

Main Results:

• lncRNA Tincr expression was significantly decreased in hypertrophic myocardial tissues and H9C2 cells.
• Re-expression of Tincr ameliorated cardiac dysfunction in hypertrophic mice.
• Identified a regulatory axis: Tincr directly targets miR-31-5p, which in turn targets PRKCE.
• Knockdown of Tincr increased cardiomyocyte size; inhibition of miR-31-5p or overexpression of PRKCE reversed this effect.

Conclusions:

• A novel Tincr-miR-31-5p-PRKCE signaling pathway is implicated in the development of cardiomyocyte hypertrophy.
• This pathway represents a potential therapeutic target for managing heart failure associated with cardiomyocyte hypertrophy.
• Further research into lncRNA-mediated regulation offers promising avenues for cardiovascular disease treatment.