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miR-24-3p induces human intervertebral disc degeneration by targeting insulin-like growth factor binding protein 5 and the ERK signaling pathway
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.lfs.2020.117288
Zhonghui Chen 1 , Ming Liu 2 , Weibing Zhang 1 , Ming Deng 1 , Yan Zhou 1 , Yaming Li 1
Affiliation  

Intervertebral disc degeneration (IDD) was associated with microRNA (miRNA) dysregulation. Therefore, we verified the hypothesis that miRNAs modulated IDD by affecting the insulin-like growth factor-binding protein 5 (IGFBP5)/extracellular signal-regulated kinase (ERK) signaling pathway. The miRNA expression profiles in nucleus pulposus (NP) cells were compared between patients with IDD and controls, and miRNA microarray and quantitative real-time PCR (RT-qPCR) assays were utilized. Luciferase reporter and Western blotting assays were performed to detect the miRNA targets. RT-qPCR confirmed that the expression level of miR-24-3p was significantly increased in degenerative NP cells. Moreover, the miR-24-3p level was positively correlated with the disc degeneration grade, and miR-24-3p significantly induced NP cell apoptosis. IGFBP5 was determined as a target of miR-24-3p, and IGFBP5 knockdown induced effects on NP cells similar to those induced by miR-24-3p. Compared with control cells, NP cells presented with miR-24-3p overexpression or IGFBP5 downregulation via shRNAs had significantly increased p-ERK and Bax expression levels. Furthermore, in vivo analysis on IDD rat model showed that the downregulation of miR-24-3p could effectively suspend IDD. These results demonstrated that miR-24-3p upregulation could promote IDD through IGFBP5 and the ERK signaling pathway.

中文翻译:


miR-24-3p通过靶向胰岛素样生长因子结合蛋白5和ERK信号通路诱导人椎间盘退变



椎间盘退变 (IDD) 与 microRNA (miRNA) 失调有关。因此,我们验证了miRNA通过影响胰岛素样生长因子结合蛋白5(IGFBP5)/细胞外信号调节激酶(ERK)信号通路来调节IDD的假设。比较 IDD 患者和对照者髓核 (NP) 细胞中 miRNA 的表达谱,并采用 miRNA 微阵列和定量实时 PCR (RT-qPCR) 检测方法。进行荧光素酶报告基因和蛋白质印迹分析来检测 miRNA 靶标。 RT-qPCR证实退变NP细胞中miR-24-3p的表达水平显着增加。此外,miR-24-3p水平与椎间盘退变程度呈正相关,并且miR-24-3p显着诱导NP细胞凋亡。 IGFBP5 被确定为 miR-24-3p 的靶标,IGFBP5 敲低对 NP 细胞产生的影响与 miR-24-3p 诱导的影响相似。与对照细胞相比,miR-24-3p过表达或通过shRNA下调IGFBP5的NP细胞p-ERK和Bax表达水平显着增加。此外,IDD大鼠模型的体内分析表明,下调miR-24-3p可以有效暂停IDD。这些结果表明,miR-24-3p上调可以通过IGFBP5和ERK信号通路促进IDD。
更新日期:2020-01-08
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