环状 NFKB1 通过海绵吸附 miR-203a-5p 调控 ERBB4 表达并促进 IL-1β 诱导的软骨细胞凋亡。
Circ-NFKB1 sponges miR-203a-5p to regulate ERBB4 expression and promotes IL-1β induced chondrocytes apoptosis.
机构信息
Department of Orthopedics, Jingjiang People's Hospital, Jingjiang, Jiangsu Province, China.
Department of Medical Imaging, Jingjiang People's Hospital, Jingjiang, Jiangsu Province, China.
出版信息
J Orthop Surg Res. 2023 Jul 25;18(1):528. doi: 10.1186/s13018-023-03990-4.
BACKGROUND
Osteoarthritis (OA) is a chronic disease of the bones and joints that commonly affects middle-aged and elderly individuals, characterized by the degeneration of articular cartilage and inflammation of the joints. The molecular mechanisms of OA urgently need to be further examined. Our study intended to uncover circ-NFKB1/miR-203a-5p/ERBB4 axis in regulating interleukin-1β (IL-1β) induced chondrocytes apoptosis.
METHODS
GSE178724, GSE79258 and GSE169077 were downloaded from Gene Expression Omibus (GEO) database and differentially expressed circRNAs, miRNAs and mRNAs were obtained by R software. Annexin V assay was used to determine cell apoptosis rate. ELISA was further performed to identify the inflammation response. Dual-luciferase reporter gene assay was conducted to examine the combination among circ-NFKB1, miR-203a-5p and ERBB4.
RESULTS
Our research demonstrated that circ-NFKB1 and ERBB4 were significantly upregulated through bioinformatic analysis. MiR-203a-5p was significantly downregulated through bioinformatic analysis. Silencing of circ-NFKB1 notably inhibited the IL-1β induced chondrocytes apoptosis and upregulated ERBB4 expression. Through prediction on bioinformatics analysis, miR-203a-5p was the target binding circ-NFKB1, and ERBB4 was the potential target of miR-203a-5p. Subsequently, these changes induced by the silencing of circ-NFKB1 were reversed upon addition of pcDNA/ERBB4.
CONCLUSIONS
Silencing circ-NFKB1 could sponge miR-203a-5p to regulate ERBB4 expression and alleviate OA progression.
背景
骨关节炎（OA）是一种常见于中老年人的骨骼和关节的慢性疾病，其特征是关节软骨退化和炎症。OA 的分子机制急需进一步研究。我们的研究旨在揭示环状 NFKB1/miR-203a-5p/ERBB4 轴在调节白细胞介素 1β（IL-1β）诱导的软骨细胞凋亡中的作用。
方法
从基因表达综合数据库（GEO）下载 GSE178724、GSE79258 和 GSE169077，使用 R 软件获得差异表达的 circRNAs、miRNAs 和 mRNAs。采用 Annexin V 检测法测定细胞凋亡率。进一步进行 ELISA 检测以鉴定炎症反应。通过双荧光素酶报告基因检测实验检测 circ-NFKB1、miR-203a-5p 和 ERBB4 之间的结合。
结果
通过生物信息学分析，我们的研究表明 circ-NFKB1 和 ERBB4 显著上调。通过生物信息学分析，miR-203a-5p 显著下调。沉默 circ-NFKB1 显著抑制 IL-1β 诱导的软骨细胞凋亡，并上调 ERBB4 表达。通过生物信息学预测分析，miR-203a-5p 是 circ-NFKB1 的靶结合物，而 ERBB4 是 miR-203a-5p 的潜在靶标。随后，沉默 circ-NFKB1 引起的这些变化在添加 pcDNA/ERBB4 后被逆转。
结论
沉默 circ-NFKB1 可以通过海绵吸附 miR-203a-5p 来调节 ERBB4 表达并缓解 OA 进展。
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