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Abstract：
Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in various diseases has been verified. However, the underlying mechanism of CDKN2B-AS1 contributes to the development of allergic rhinitis (AR) remains unknown. To evaluate the impact of CDKN2B-AS1 on AR, BALB/c mice were sensitized by intraperitoneal injection of normal saline containing ovalbumin (OVA) and calmogastrin to establish an AR model. Nasal rubbing and sneezing were documented after the final OVA treatment. The concentrations of IgE, IgG1, and inflammatory elements were quantified using ELISA. Hematoxylin and eosin (H&E) staining and immunofluorescence were used to assess histopathological variations and tryptase expression, respectively. StarBase, TargetScan and luciferase reporter assays were applied to predict and confirm the interactions among CDKN2B-AS1, miR-98-5p, and SOCS1. CDKN2B-AS1, miR-98-5p, and SOCS1 levels were assessed by quantitative real-time PCR (qRT-PCR) or western blotting. Our results revealed that CDKN2B-AS1 was obviously over-expressed in the nasal mucosa of AR patients and AR mice. Down-regulation of CDKN2B-AS1 significantly decreased nasal rubbing and sneezing frequencies, IgE and IgG1 concentrations, and cytokine levels. Furthermore, down-regulation of CDKN2B-AS1 also relieved the pathological changes in the nasal mucosa, and the infiltration of eosinophils and mast cells. Importantly, these results were reversed by the miR-98-5p inhibitor, whereas miR-98-5p directly targeted CDKN2B-AS1, and miR-98-5p negatively regulated SOCS1 level. Our findings demonstrate that down-regulation of CDKN2B-AS1 improves allergic inflammation and symptoms in a murine model of AR through the miR-98-5p/SOCS1 axis, which provides new insights into the latent functions of CDKN2B-AS1 in AR treatment.
摘要：
长链非编码RNA细胞周期蛋白依赖性激酶抑制剂2B反义RNA1(CDKN2B-AS1)在多种疾病中的作用已得到验证。然而,CDKN2B-AS1促进变应性鼻炎(AR)发展的潜在机制尚不清楚.为了评估CDKN2B-AS1对AR的影响，BALB/c小鼠腹腔注射含卵清蛋白（OVA）和钙胃泌素的生理盐水致敏，建立AR模型。在最后的OVA治疗后记录鼻腔摩擦和打喷嚏。IgE的浓度,使用ELISA定量IgG1和炎性元件。苏木精和伊红（H＆E）染色和免疫荧光用于评估组织病理学变异和类胰蛋白酶表达，分别。StarBase,TargetScan和荧光素酶报告基因测定用于预测和确认CDKN2B-AS1，miR-98-5p，SOCS1。CDKN2B-AS1,miR-98-5p,通过定量实时PCR(qRT-PCR)或蛋白质印迹法评估SOCS1水平。我们的结果表明，CDKN2B-AS1在AR患者和AR小鼠的鼻粘膜中明显过表达。CDKN2B-AS1的下调显着降低了鼻腔摩擦和打喷嚏的频率，IgE和IgG1浓度，和细胞因子水平。此外，CDKN2B-AS1的下调也缓解了鼻黏膜的病理变化，嗜酸性粒细胞和肥大细胞的浸润。重要的是,这些结果被miR-98-5p抑制剂逆转，而miR-98-5p直接靶向CDKN2B-AS1，miR-98-5p负调控SOCS1水平。我们的发现表明，CDKN2B-AS1的下调通过miR-98-5p/SOCS1轴改善了AR小鼠模型的过敏性炎症和症状，这为CDKN2B-AS1在AR治疗中的潜在功能提供了新的见解。
