Circ0061052 regulation of FoxC1/Snail pathway via miR-515-5p is involved in the epithelial-mesenchymal transition of epithelial cells during cigarette smoke-induced airway remodeling
Circ0061052 regulation of FoxC1/Snail pathway via miR-515-5p is involved in the epithelial-mesenchymal transition of epithelial cells during cigarette smoke-induced airway remodeling
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Circ0061052通过miR-515-5p调节FoxC1/Snail通路参与香烟烟雾诱导的气道重塑过程中上皮细胞的上皮间质转化
DOI：
10.1016/j.scitotenv.2020.141181
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发表时间：
2020-12-01
影响因子：
9.8
通讯作者：
Shi, Aimin
中科院分区：
文献类型：
--
作者：
Ma, Huimin;Lu, Lu;Shi, Aimin
环状RNA（circRNA）已被证明广泛参与多种肺部疾病。香烟烟雾（CS）可诱导慢性阻塞性肺疾病（COPD）气道重塑中的上皮-间质转化（EMT），但circRNA在其中的作用及机制尚不清楚。在这项研究中，我们的目的是确定是否circ 0061052参与人支气管上皮细胞（HBE）的EMT及其发挥生物学作用的潜在机制。香烟烟雾提取物（CSE）引起HBE细胞EMT指标升高和circ 0061052增加。Circ 0061052具有环状结构，主要存在于HBE细胞的细胞质中。我们使用生物信息学、荧光素酶报告基因和qRT-PCR分析了circ 0061052和miR-515- 5 p之间的调控关系。我们发现circ 0061052主要分布在细胞质中，并与miR-515- 5 p竞争结合，充当miR-515- 5 p的海绵。荧光素酶报告基因显示miR-515- 5 p与FoxC 1 mRNA的3 'UTR区域结合以抑制其转录。对于HBE细胞，miR-515- 5 p的过表达拮抗CSE诱导的EMT。此外，circ 0061052通过竞争性结合miR-515- 5 p来调节FoxC 1/Snail的表达。当circ 0061052 siRNA和miR-515- 5 p抑制剂共转染HBE细胞时，抑制剂逆转了circ 0061052 siRNA降低EMT的作用。小鼠长期暴露于CS诱导circ 0061052水平升高、miR-515- 5 p水平降低和肺组织中的EMT，这引起功能障碍和气道阻塞。总之，结果表明，通过FoxC 1/Snail调节轴调节miR-515- 5 p，circ 0061052参与了CS诱导的EMT和COPD气道重塑。(C)2020 Elsevier B. V.保留所有权利。
Circular RNA (circRNA) has been shown to be widely involved in a variety of lung diseases. Cigarette smoke (CS) may induce epithelial-mesenchymal transition (EMT) of airway remodeling in chronic obstructive pulmonary disease (COPD), however, in which the roles and mechanisms of circRNA have not been elucidated. In this study, we aimed to determine whether circ0061052 is involved in the EMT of human bronchial epithelial (HBE) cells and its potential mechanism for playing a biological role. Cigarette smoke extract (CSE) caused elevated EMT indicators and the increases of circ0061052 in HBE cells. Circ0061052 has a ring structure and is mainly present in the cytoplasm of HBE cells. We analyzed the regulatory relationship between circ0061052 and miR-515-5p using bioinformatics, a luciferase reporter gene, and qRT-PCR. We found that circ0061052 is mainly distributed in the cytoplasm and competitively binds to miR-515-5p, acting as a sponge for miR-515-5p. The luciferase reporter gene showed that miR-515-5p binds to the 3'UTR region of FoxC1 mRNA to inhibit its transcription. For HBE cells, overexpression of miR-515-5p antagonized the CSE-induced EMT. In addition, circ0061052 acts by binding miR-515-5p competitively to regulate the expression of FoxC1/Snail. When circ0061052 siRNA and miR-515-5p inhibitor were co-transfected into HBE cells, the inhibitor reversed the effect of circ0061052 siRNA on reducing EMT. Chronic exposure of mice to CS induced increases of circ0061052 levels, decreases of miR-515-5p levels, and the EMT in lung tissue, which caused dysfunction and airway obstruction. Overall, the results show that, by regulating miR-515-5p through a FoxC1/Snail regulatory axis, circ0061052 is involved in the CS-induced EMT and airway remodeling in COPD. (C) 2020 Elsevier B.V. All rights reserved.