Conclusions
In summary, our study provides evidence that miR-4478 may aggravate IVDD through its target gene MTH1 by accelerating oxidative stress in NPCs and demonstrates that miR-4478 has therapeutic potential in IVDD treatment.
Methods
We analyzed miRNA microarray datasets to identify differentially expressed miRNAs in IVDD progression and conducted quantitative real-time polymerase chain reaction and fluorescence in situ hybridization analysis to further confirm the differential expression of miR-4478 in nucleus pulposus (NP) tissues of patients diagnosed with IVDD. Using public databases of miRNA-mRNA interactions, we predicted the target genes of miR-4478, and subsequent flow cytometry and western blot analyses demonstrated the effect of MTH1 in H 2 O 2 -induced nucleus pulposus cells (NPCs) apoptosis. Finally, miR-4478 inhibitor was injected into NP tissues of the IVDD mouse model to explore the effect of miR-4478 in vivo.
Results
miR-4478 was upregulated in NP tissues from IVDD patients. Silencing of miR-4478 inhibits H 2 O 2 -induced NPCs apoptosis. MTH1 was identified as a target gene for miR-4478, and miR-4478 regulates H 2 O 2 -induced NPCs apoptosis by modulating MTH1. In addition, downregulation of miR-4478 alleviated IVDD in a mouse model. Conclusions: In summary, our study provides evidence that miR-4478 may aggravate IVDD through its target gene MTH1 by accelerating oxidative stress in NPCs and demonstrates that miR-4478 has therapeutic potential in IVDD treatment.