Bioinformatics analysis integrating metabolomics of m⁶A RNA microarray in intervertebral disc degeneration

Aim: To explore the potential functions and mechanism of N⁶.methyladenosine (m⁶A) abnormality of RNAs in nucleus pulposus from the intervertebral disc degeneration (IDD). Materials & methods: We performed rat model, m⁶A epitranscriptomic microarray, bioinformatics analysis and metabolomics. Results: In IDD, most of the differentially methylated RNAs showed a significant demethylation situation. The competing endogenous RNA network LOC102555094/miR-431/GSK-3β combining downstream Wnt pathway were identified in bioinformatics analysis. For metabolomics, activation of Wnt pathway led to reprogramming of glucose metabolism and enzyme activation of PKM2. Finally, quantitative real-time PCR and methylated RNA immunoprecipitation coupled with quantitative real-time PCR revealed the positive correlation between demethylation of LOC102555094 and expression of both FTO and ZFP217. Conclusion:LOC102555094 might be demethylated by ZFP217, activating FTO and LOC102555094/miR-431/GSK-3β/Wnt played a crucial role in IDD.