Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, PR China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, PR China; Department of Critical Care Medicine, Tsinghua University Affiliated Beijing Tsinghua Changgung Hospital, 168 Litang Road, Changping District, Beijing, 102218, PR China.
Int J Biochem Cell Biol. 2022 Dec;153:106313. doi: 10.1016/j.biocel.2022.106313. Epub 2022 Oct 17.
Acute respiratory distress syndrome (ARDS) is a common and serious respiratory illness with substantial morbidity and mortality. Circular RNAs have been demonstrated to participate in various diseases processes. However, the biological function and mechanism of most circular RNAs have not been elucidated in ARDS. In this study, we found that circUBXN7 was significantly increased in lipopolysaccharide (LPS)-induced A549 and Beas-2B cell injury. Inhibition of circUBXN7 significantly promoted cell proliferation and reduced cell apoptosis, while overexpression of circUBXN7 suppressed cell proliferation and accelerated cell apoptosis in LPS-induced A549 and Beas-2B cells. CircUBXN7 acted as a sponge for miR-622, and miR-622 rescued the effect of circUBXN7 on cell proliferation and apoptosis. We also found that IL6ST was a target gene of miR-622, and the expression of IL6ST was indirectly regulated by circUBXN7. Furthermore, western blotting indicated that the JAK1/STAT3 signaling pathway was involved in the circUBXN7/miR-622/IL6ST axis in LPS-induced A549 and Beas-2B cell injury. Overall, our study suggested that circUBXN7 suppressed cell proliferation and facilitated cell apoptosis by sponging miR-622 and regulating IL6ST, to activate the JAK1/STAT3 signaling pathway in LPS-induced A549 and Beas-2B cell injury. CircUBXN7 might therefore be a potential biomarker for ARDS, and dysregulation of circUBXN7 may be involved in the pathogenesis of ARDS.
急性呼吸窘迫综合征(ARDS)是一种常见且严重的呼吸系统疾病,具有较高的发病率和死亡率。环状 RNA 已被证明参与多种疾病的发生发展过程。然而,在 ARDS 中,大多数环状 RNA 的生物学功能和机制尚未阐明。在本研究中,我们发现脂多糖(LPS)诱导的 A549 和 Beas-2B 细胞损伤中 circUBXN7 显著增加。抑制 circUBXN7 显著促进细胞增殖并减少细胞凋亡,而过表达 circUBXN7 则抑制 LPS 诱导的 A549 和 Beas-2B 细胞增殖并加速细胞凋亡。circUBXN7 作为 miR-622 的海绵体,miR-622 挽救了 circUBXN7 对细胞增殖和凋亡的影响。我们还发现 IL6ST 是 miR-622 的靶基因,而 IL6ST 的表达是由 circUBXN7 间接调节的。此外,Western blot 表明 JAK1/STAT3 信号通路参与 LPS 诱导的 A549 和 Beas-2B 细胞损伤中的 circUBXN7/miR-622/IL6ST 轴。总之,我们的研究表明,circUBXN7 通过海绵吸附 miR-622 并调节 IL6ST 抑制细胞增殖并促进细胞凋亡,从而激活 LPS 诱导的 A549 和 Beas-2B 细胞损伤中的 JAK1/STAT3 信号通路。circUBXN7 因此可能成为 ARDS 的潜在生物标志物,而 circUBXN7 的失调可能参与 ARDS 的发病机制。