Knockdown circ_0040414 inhibits inflammation, apoptosis and promotes the proliferation of cardiomyocytes via miR‐186‐5p/PTEN/AKT axis in chronic heart failure
Yanling Feng, Biao Yan, Hongji Cheng, Jinlei Wu, Qinxiu Chen, Yuexing Duan, Peng Zhang, Dong Zheng, Guixiong Lin, Yufeng Zhuo
Abstract
Previous studies have shown that circ_0040414 is highly expressed in the blood of patients with heart failure (HF), which suggests that circ_0040414 is associated with heart failure (HF). However, the functional involvement of circ_0040414 in HF and its potential mechanism remains unclear. Consistent with previous studies, our study showed that the expression of circ_0040414 in the peripheral blood of patients with chronic heart failure (CHF) was significantly higher than that of healthy control, which indicated that circ_0040414 could be used as a diagnostic biomarker in patients with CHF. In cardiomyocytes, circ_0040414 increased the level of proapoptotic proteins Bax, cleaved-caspase 3 and reduced the expression of antiapoptotic protein Bcl-2. It also promoted inflammatory factors IL-6, TNF-α, and IL-β, but inhibited cell proliferation. In terms of mechanism, circ_0040414 upregulated the expression of phosphatase and tensin homolog (PTEN) through sponging miR-186-5p to inhibit AKT signaling activity. Our study uncovered a novel role and the mechanism of circ_0040414 in controlling CHF, enriched the molecular regulatory network in CHF, and may provide a possible strategy for the treatment of CHF.