Bioinformatics Analysis Integrating Metabolomics of m <sup>6</sup> A RNA Microarray in Intervertebral Disc Degeneration
Xiaoshuai Wang, Ningning Chen, ZeFeng Du, Zemin Ling, Penghui Zhang, Jiaming Yang, Mohammed Khaleel, Anthony Khoury, Jianwen Li, Songbo Li, Haoyang Huang, Xinwei Zhou, Yueyin Han, Fuxin Wei
Abstract
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.