Abstract This study aimed to investigate the expression and role of microRNA-449a (miR-449a) in inflammatory bowel disease (IBD) in children, and further to explore the underlying mechanism. To study the role of miR-449a in IBD development, an in vitro inflammatory model of IBD was conducted by stimulating the normal intestinal epithelial cells Caco-2 with 2% dextran sulfate sodium (DSS). The results showed that the miR-449a level was significantly higher in children with IBD than that in children without IBD. Notch1 was a direct target gene of miR-449a. The increased levels of TNF-α, IL-1β and IL-6, reduced cell viability and enhanced cell apoptosis in Caco-2 cells caused by DSS administration were significantly inhibited by miR-449a inhibition. Besides, DSS significantly decreased the level of Notch1, Hes-1, Hey-1 and Bcl-2, and increased Bax expression, and these changes were prevented by miR-449a inhibitor. Importantly, all the effects of miR-449a inhibitor on Caco-2 cells were eliminated by Notch1 gene silencing. In conclusion, the data of our study indicated that miR-449a was up-regulated in IBD in children, and miR-449a inhibitor could inhibit inflammatory response and cell apoptosis by targeting Notch1 in IBD in vitro. The miR-449a/Notch1 axis might be a novel target for IBD treatment.

中文翻译：

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microRNA-449a在儿童炎症性肠病进展中的作用

摘要 本研究旨在探讨microRNA-449a（miR-449a）在儿童炎症性肠病（IBD）中的表达和作用，并进一步探讨其潜在机制。为了研究 miR-449a 在 IBD 发展中的作用，通过用 2% 葡聚糖硫酸钠 (DSS) 刺激正常肠上皮细胞 Caco-2 来进行 IBD 的体外炎症模型。结果显示，IBD患儿的miR-449a水平显着高于非IBD患儿。Notch1 是 miR-449a 的直接靶基因。miR-449a 抑制显着抑制了 DSS 给药引起的 Caco-2 细胞 TNF-α、IL-1β 和 IL-6 水平升高、细胞活力降低和细胞凋亡增强。此外，DSS 显着降低 Notch1、Hes-1、Hey-1 和 Bcl-2 的水平，Bax 表达增加，而这些变化被 miR-449a 抑制剂阻止。重要的是，通过 Notch1 基因沉默消除了 miR-449a 抑制剂对 Caco-2 细胞的所有影响。总之，我们的研究数据表明 miR-449a 在儿童 IBD 中上调，miR-449a 抑制剂可以在体外通过靶向 IBD 中的 Notch1 抑制炎症反应和细胞凋亡。miR-449a/Notch1 轴可能是 IBD 治疗的新靶点。和 miR-449a 抑制剂可以在体外通过靶向 IBD 中的 Notch1 来抑制炎症反应和细胞凋亡。miR-449a/Notch1 轴可能是 IBD 治疗的新靶点。和 miR-449a 抑制剂可以在体外通过靶向 IBD 中的 Notch1 来抑制炎症反应和细胞凋亡。miR-449a/Notch1 轴可能是 IBD 治疗的新靶点。