Knockdown circ_0040414 inhibits inflammation, apoptosis and promotes the proliferation of cardiomyocytes via miR-186-5p/PTEN/AKT axis in chronic heart failure

敲低 circ_0040414 可通过 miR-186-5p/PTEN/AKT 轴抑制慢性心力衰竭中的炎症、凋亡并促进心肌细胞增殖

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作者: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.

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