Knockdown of circRNA_0030042 Attenuates Heart Failure via miR-568/PRG4 Pathway

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiology

Background:

• Heart failure is a leading global cause of death, characterized by cardiac structural and functional abnormalities.
• Circular RNAs (circRNAs) are emerging as critical regulators in various diseases, but their role in heart failure remains largely unexplored.
• circRNA_0030042, derived from the FOXO1 gene, is a newly identified circRNA with an unknown function in heart failure.

Purpose of the Study:

• To investigate the role and underlying mechanism of circRNA_0030042 in the progression of heart failure.
• To explore the potential of targeting circRNA_0030042 as a therapeutic strategy for heart failure.

Main Methods:

• Established an in vitro heart failure model using H2O2-induced AC16 cells and an in vivo model using transverse aortic constriction (TAC) in mice.
• Assessed the expression levels of circRNA_0030042 in patient blood samples and cell/animal models.
• Utilized knockdown techniques for circRNA_0030042 and analyzed its effects on cell viability, apoptosis, ferroptosis markers (ROS, MDA, GSH, iron levels), and key proteins (SLC7A11, GPX4).
• Investigated the interaction between circRNA_0030042, miR-568, and PRG4 using molecular biology techniques.
• Evaluated cardiac function, myocardial injury markers (cTnI, CK-MB, BNP), and cardiac histopathology in TAC mice.

Main Results:

• circRNA_0030042 expression was significantly upregulated in heart failure patients and H2O2-induced AC16 cells.
• Knockdown of circRNA_0030042 suppressed apoptosis, enhanced viability, reduced ferroptosis, and increased protective protein expression in H2O2-treated AC16 cells.
• circRNA_0030042 positively regulated PRG4 expression by sponging miR-568, forming the circRNA_0030042/miR-568/PRG4 pathway.
• In vivo, circRNA_0030042 knockdown improved cardiac function, reduced myocardial injury, alleviated histopathological damage, and restored protective protein levels in TAC mice.

Conclusions:

• circRNA_0030042 plays a detrimental role in heart failure progression by promoting ferroptosis via the miR-568/PRG4 pathway.
• Targeting circRNA_0030042 offers a potential therapeutic approach to attenuate heart failure and improve cardiac function.