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.

中文翻译：

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敲低 circ_0040414 在慢性心力衰竭中通过 miR-186-5p/PTEN/AKT 轴抑制炎症、细胞凋亡并促进心肌细胞增殖

既往研究表明，circ_0040414在心力衰竭（HF）患者的血液中高表达，提示circ_0040414与心力衰竭（HF）有关。然而，circ_0040414 在 HF 中的功能参与及其潜在机制仍不清楚。与以往研究一致，我们的研究表明，慢性心力衰竭（CHF）患者外周血中circ_0040414的表达明显高于健康对照组，这表明circ_0040414可作为CHF患者的诊断生物标志物。 . 在心肌细胞中，circ_0040414 增加了促凋亡蛋白 Bax、cleaved-caspase 3 的水平并降低了抗凋亡蛋白 Bcl-2 的表达。它还促进炎症因子 IL-6、TNF-α 和 IL-β，但抑制细胞增殖。机制上，circ_0040414通过海绵化miR-186-5p抑制AKT信号活性，上调磷酸酶和张力蛋白同源物（PTEN）的表达。我们的研究揭示了circ_0040414在控制CHF中的新作用和机制，丰富了CHF的分子调控网络，可能为CHF的治疗提供可能的策略。