MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration
MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration
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DOI：
10.1159/000438630
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Zou, Debo
中科院分区：
文献类型：
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作者：
Ma, Jin Feng;Zang, Li Na;Zou, Debo
背景：脊柱退行性疾病是世界范围内的主要健康问题和社会负担。椎间盘退变是脊柱退行性疾病的病理基础，其特征是多种因素引起的过度凋亡导致髓核细胞丢失。MicroRNA（miRNAs）已被报道在功能上参与细胞凋亡的控制。研究方法：通过计算分析和荧光素酶分析确定miR-125 a的作用靶点，并通过细胞培养、转染等方法证实这种关系。测序用于确定每位参与者的基因型。结果如下：我们证实了之前的报道，rs 12976445多态性的次要等位基因（T）的存在显著下调了髓核细胞中miR-125 a的表达水平，导致其靶基因的抑制效率降低。我们还使用双荧光素酶报告系统验证了TP 53 INP 1作为髓核细胞中miR-125 a的靶点，并且miR-125 a的转染显著降低了TP 53 INP 1的表达。TP 53 INP 1的表达水平在基因型为CT或TT的髓核细胞中显著低于基因型为CC的髓核细胞，并且细胞凋亡率在CC组中始终低于从携带至少一个rs 12976445多态性的次要等位基因的个体收集的髓核细胞。为研究rs 12976445基因多态性与IDD发病的关系，我们选取了242例IDD患者和278例正常对照者，发现rs 12976445基因型在IDD组和正常对照组中的分布差异有统计学意义（OR = 2.69，95% C.I. = 1.88-3.83，p < 0.0001）。总之，rs 12976445多态性与中国人群IDD的风险显著相关。结论：miR-125 a是IDD患者治疗的潜在靶点。版权所有（C）2016 S. Karger AG，巴塞尔
Background: Spinal degenerative diseases are a major health problem and social burden worldwide. Intervertebral disc degeneration (IDD) is the pathological basis of spinal degenerative diseases and is characterized by loss of nucleus pulposus cells due to excessive apoptosis caused by various factors. MicroRNAs (miRNAs) have been reported to be functionally involved in the control of apoptosis. Methods: computational analysis and luciferase assay were used to identify the target of miR-125a, and cell culture, transfection were used to confirm such relationship. Sequencing was used to determine the genotype of each participant. Results: We confirmed the previous report that the presence of the minor allele (T) of rs12976445 polymorphism significantly downregulated the expression level of miR-125a in nucleus pulposus cells, leading to less efficient inhibition of its target gene. We also validated TP53INP1 as a target of miR-125a in nucleus pulposus cells using a dual luciferase reporter system, and the transfection of miR-125a significantly reduced the expression of TP53INP1. The expression level of TP53INP1 was significantly lower in nucleus pulposus cells genotyped as CT or TT than in those genotyped as CC, and the apoptosis rate was consistently lower in the CC group than in the nucleus pulposus cells collected from individuals carrying at least one minor allele of rs12976445 polymorphism. To study the association between rs12976445 polymorphism and the risk of IDD, we enrolled 242 patients diagnosed with IDD and 278 normal controls, and significant differences were noted regarding the genotype distribution of rs12976445 between the IDD and the control groups (OR = 2.69, 95% C.I. = 1.88-3.83, p < 0.0001). In summary, rs12976445 polymorphism is significantly associated with the risk of IDD in the Chinese population. Conclusion: The present study indicated that miR-125a is a promising potential target for patients with IDD in clinical practice. Copyright (C) 2016 S. Karger AG, Basel