MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration.

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.