INTRODUCTION This study aimed to elucidate the biological implication of miR-937 in cigarette smoke extract (CSE)-induced human bronchial epithelial (HBE) cells and to further investigate its possible regulatory mechanism. METHODS Public datasets were downloaded to identify differentially expressed genes and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis in chronic obstructive pulmonary disease (COPD). Online prediction site and luciferase reporter assay were applied to determine the target correlation between miR-937 and IL1B. RT-qPCR, Western blot and Enzyme-Linked Immunosorbent Assays (ELISA) analyses were used to evaluate the expressions of indicated molecules. HBE cells were exposed with CSE (20 μg/mL) to construct the in vitro COPD model. Cell proliferation and apoptosis were measured through cell counting kit 8 and Annexin-V/propidium iodide (PI) staining assays. RESULTS IL1B was found to be up-regulated in COPD samples compared with healthy controls and had a high correlation with the TNF and IL-17 pathways according to the data from GSE57148. Moreover, IL1B was predicted to be a target of miR-937, and it was negatively regulated by miR-937. CSE treatment reduced the miR-937 expression, meanwhile decreased the HBE cells proliferation, enhanced cells apoptosis, and elevated the expression of IL-6, IL-17, and TNF-α. Moreover, in the CSE model, upregulation of miR-937 promoted cells viability, restrained cells apoptosis, and decreased levels of IL-6, IL-17, and TNF-α were noted, which could be abolished by overexpression IL1B. In contrast, inhibiting miR-937 impeded cells proliferation, promoted cells apoptosis and elevated levels of IL-6, IL-17 and TNF-α, which could be rescued by IL1B-knockdown in CSE-induced HBEs. CONCLUSIONS These findings suggest that miR-937 plays a protective role on the HBEs after CSE damage, which may be achieved via targeting IL1B and inhibiting the TNF-α/IL-17 signaling pathway.

中文翻译：

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miR-937 通过靶向 IL1B 和调节 TNF-α/IL-17 信号通路，在香烟烟雾提取物诱导的人支气管上皮细胞中充当炎症抑制剂。

引言 本研究旨在阐明 miR-937 在香烟烟雾提取物 (CSE) 诱导的人支气管上皮 (HBE) 细胞中的生物学意义，并进一步研究其可能的调节机制。方法下载公共数据集以识别差异表达的基因，并进行京都基因和基因组百科全书（KEGG）在慢性阻塞性肺疾病（COPD）中的通路富集分析。应用在线预测站点和荧光素酶报告基因测定来确定 miR-937 和 IL1B 之间的靶标相关性。RT-qPCR、蛋白质印迹和酶联免疫吸附测定 (ELISA) 分析用于评估指定分子的表达。HBE 细胞暴露于 CSE (20 μg/mL) 以构建体外 COPD 模型。通过细胞计数试剂盒 8 和膜联蛋白-V/碘化丙啶 (PI) 染色测定法测量细胞增殖和凋亡。结果 根据 GSE57148 的数据，发现与健康对照相比，COPD 样本中 IL1B 上调，并且与 TNF 和 IL-17 通路具有高度相关性。此外，IL1B 被预测为 miR-937 的靶点，并受到 miR-937 的负调控。CSE处理降低了miR-937的表达，同时降低了HBE细胞的增殖，增强了细胞凋亡，并提高了IL-6、IL-17和TNF-α的表达。此外，在 CSE 模型中，miR-937 的上调促进了细胞活力，抑制了细胞凋亡，并注意到 IL-6、IL-17 和 TNF-α 水平降低，这可以通过过表达 IL1B 消除。相比之下，抑制 miR-937 会阻碍细胞增殖，促进细胞凋亡并提高 IL-6、IL-17 和 TNF-α 的水平，这可以通过 CSE 诱导的 HBE 中的 IL1B 敲低来挽救。结论 这些发现表明 miR-937 在 CSE 损伤后对 HBE 发挥保护作用，这可能通过靶向 IL1B 和抑制 TNF-α/IL-17 信号通路来实现。