CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1.

Abstract

OBJECTIVE:

Sepsis is a predominant reason for the growing morbidity and mortality in the world. The role of circular RNAs (CircRNAs) is actively researched in sepsis. In this study, we attempt to find out the effect of CircRNA protein tyrosine kinase 2 (circPTK2) on cardiomyocyte apoptosis in septic mice.

METHODS:

Septic mouse model was established by cecal ligation and puncture. Then circPTK2 expression was detected and the role of circPTK2 in myocardial damage was assessed after circPTK2 expression was silenced using Ad-sh-circHIPK3. The subcellular localization of circPTK2 was analyzed. Besides, the binding relation between circPTK2 and microRNA (miR)-29b-3p and between miR-29b-3p and BCL2 antagonist/killer 1 (BAK1) was verified. The expression of miR-29b-3p and BAK1 in the myocardium was detected. Functional rescue was conducted to evaluate the role of miR-29b-3p and BAK1 in cardiomyocyte apoptosis in septic mice.

RESULTS:

CircPTK2 was highly expressed in the myocardium of septic mice, while circPTK2 silencing relieved the cardiac function and reduced inflammatory reaction and cardiomyocyte apoptosis of septic mice. Mechanically, circPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level. Inhibition of miR-29b-3p and BAK1 overexpression could counteract the protective role of circPTK2 silencing in the myocardium of septic mice.

CONCLUSION:

CircPTK2 is overexpressed in the myocardium of septic mice. CircPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level, to promote cardiomyocyte apoptosis, inflammatory response, and myocardial damage of the myocardium of septic mice.

• Authors: Hui Xiao, Quanzhu Fu, Li Min
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 183 Issue 5 Pg. 552-565 ( 2022) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 34915498 (Publication Type: Journal Article)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• Bak1 protein, mouse
• MicroRNAs
• RNA, Circular
• RNA, Messenger
• bcl-2 Homologous Antagonist-Killer Protein

Topics

• Animals
• Apoptosis (genetics)
• Mice
• MicroRNAs (genetics, metabolism)
• Myocytes, Cardiac (metabolism)
• RNA, Circular (genetics)
• RNA, Messenger (metabolism)
• Sepsis (genetics, metabolism)
• bcl-2 Homologous Antagonist-Killer Protein (genetics, metabolism)