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

Abstract

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Revealing Landscape of Competing Endogenous RNA Networks in Sepsis-Induced Cardiovascular Diseases

“…The circRNA-mediated ceRNA networks regulate cardiovascular toxicity in sepsis, as shown in Table 3 (Ref. [ 65 , 66 , 67 , 68 ]) and Fig. 3 .…”

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

“…For example, altering circ-fatty acid desaturase 2 or circ_0001679 at the gene level can inhibit sepsis-induced ALI progression 6,12 . CircRNA protein tyrosine kinase 2 (circPTK2) has attracted academic attention in the aspect of malignancy [13][14][15] and has also been studied to mediate Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/ eukaryotic initiation factor 5A axis-mediated ATP efflux apoptosis and inflammatory response in sepsis-induced myocardial injury 16 . Notably, circPTK2 can also regulate sepsis-induced microglial activation and apoptosis in the hippocampus 17 .…”