Background

Chronic rhinosinusitis is an intractable symptom that influences daily lives of patients. miR-1287-5p was discovered to play a suppressive role in cervical cancer and HBV-related infection.

Purpose

This study investigated the potential role of miR-1287-5p in the in-vitro model of chronic rhinosinusitis.

Methods

GSE169376 dataset was analyzed and differential miRNAs in nasal mucosa tissues in the chronic rhinosinusitis group were screened out. LPS was used to treat HNECs for 12h, 24h and 48h. Cells underwent LPS treatment after SNAI1 downregulation, miR-1287-5p upregulation or pretreatment of the HMGB1 inhibitor, Glycyrrhizin. RT-PCR was used to measure the RNA expression of miR-1287-5p, SNAI1 and HMGB1. ELISA was used for the detection of IL-6, IL-8, TNF-α changes. Targetscan and starBase were used to predict the targets (SNAI1 and HMGB1) of miR-1287-5p. Dual-luciferase reporter assays were applied to validate this. Western blot was used to analyze the protein changes of Snai1, Vimentin, E-cadherin and HMGB1.

Results

miR-1287-5p was downregulated in the chronic rhinosinusitis group and decreased after LPS treatment in HNECs. The upregulation of miR-1287-5p inhibited IL-6, IL-8, TNF-α and EMT. miR-1287-5p targeted and inhibited SNAI1 and HMGB1. SNAI1 downregulation led to inhibition in EMT while loss of HMGB1 contributed to the decrease in pro-inflammatory cytokines. Knockdown of SNAI1 decreased HMGB1, resulting in the reduction of pro-inflammatory cytokines while HMGB1 inhibitor reduced SNAI1 and thus suppressed the EMT process.

Conclusion

miR-1287-5p downregulation was associated with chronic rhinosinusitis and its upregulation inhibited the EMT and inflammation in LPS-induced HNECs through Snai1/HMGB1 pathway.

中文翻译：

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miR-1287-5p 上调抑制 LPS 诱导的人鼻上皮细胞 (HNECs) 中的 EMT 和促炎细胞因子

背景

慢性鼻窦炎是一种影响患者日常生活的顽固症状。发现 miR-1287-5p 在宫颈癌和 HBV 相关感染中发挥抑制作用。

目的

本研究调查了 miR-1287-5p 在慢性鼻窦炎体外模型中的潜在作用。

方法

分析GSE169376数据集，筛选出慢性鼻窦炎组鼻黏膜组织中的差异miRNA。LPS用于治疗HNECs 12h、24h和48h。在 SNAI1 下调、miR-1287-5p 上调或 HMGB1 抑制剂甘草甜素预处理后，细胞接受了 LPS 处理。RT-PCR用于测量miR-1287-5p、SNAI1和HMGB1的RNA表达。ELISA用于检测IL-6、IL-8、TNF-α的变化。Targetscan 和starBase 用于预测miR-1287-5p 的目标（SNAI1 和HMGB1）。应用双荧光素酶报告基因测定来验证这一点。Western印迹用于分析Snai1、Vimentin、E-cadherin和HMGB1的蛋白变化。

结果

miR-1287-5p 在慢性鼻窦炎组中下调，并且在 HNEC 中 LPS 治疗后降低。miR-1287-5p 的上调抑制 IL-6、IL-8、TNF-α 和 EMT。miR-1287-5p 靶向并抑制 SNAI1 和 HMGB1。SNAI1 下调导致 EMT 的抑制，而 HMGB1 的缺失导致促炎细胞因子的减少。SNAI1 的敲低降低了 HMGB1，导致促炎细胞因子减少，而 HMGB1 抑制剂降低了 SNAI1，从而抑制了 EMT 过程。

结论

miR-1287-5p 下调与慢性鼻窦炎相关，其上调通过 Snai1/HMGB1 通路抑制 LPS 诱导的 HNEC 中的 EMT 和炎症。