Knockdown circ_0040414 inhibited inflammatory, apoptosis and promoted proliferation of cardiomyocyte via miR-186/PTEN/AKT pathway in chronic heart failure

Abstract Background Previous studies have found that the expression of circ_0040414 is elevated in heart failure (HF) patients, but the role and mechanism of circ_0040414 in HF are not yet known. The purpose of this study is to clarify the role of circ_0040414 in chronic HF (CHF) and its potential mechanism for regulating the progression of CHF. Methods Peripheral blood samples of patients with chronic heart failure and normal people were collected to detect the expression difference of circ_0040414; ROC curve was made to evaluate the value of circ_0040414 in the diagnosis of CHF; CCK8 method was implemented to detect the speed of cell proliferation; flow cytometry was performed to detect the degree of cell apoptosis; ELISA assay was used to detect the inflammatory cytokines IL-6, TNF-α and IL-β secreted by cells; circinteractome and starbase databases were used to analyze the downstream target molecules of circ_0040414 and miR-186, respectively; RT-qPCR and western blot were implemented to evaluate the expression levels of RNA and protein, respectively. Results We found that the expression of circ_00404141 in the peripheral blood of CHF patients is significantly higher than that of normal people, and it has a high diagnostic value for CHF. Circ_00404141 promotes cardiomyocyte apoptosis and inflammation, while inhibiting the proliferation of cardiomyocytes. In terms of mechanism, circ_00404141 promotes the expression of Phosphatase and Tensin Homolog (PTEN) through sponge miR-186 and inhibits AKT signal activity. Conclusion We clarified that silencing circ_00404141 promotes cardiomyocyte proliferation through miR-186/PTEN/AKT signal axis, inhibits cell apoptosis and inflammation.