Bioinformatics Analysis Integrating Metabolomics of m ⁶ A RNA Microarray in Intervertebral Disc Degeneration

Abstract

<jats:p> Aim: To explore the potential functions and mechanism of N<jats:sup>6</jats:sup>.methyladenosine (m<jats:sup>6</jats:sup>A) abnormality of RNAs in nucleus pulposus from the intervertebral disc degeneration (IDD). Materials &amp; methods: We performed rat model, m<jats:sup>6</jats:sup>A 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. </jats:p>

Glycine‐Serine‐Threonine Metabolic Axis Delays Intervertebral Disc Degeneration through Antioxidant Effects: An Imaging and Metabonomics Study

“…In addition, marker metabolites in the late stage of degeneration were mainly involved in sugar metabolism pathways such as amino sugar and nucleotide sugar metabolism, proteoglycan structural metabolism, and tricarboxylic acid (TCA) cycle; protein metabolism pathways such as cysteine and methionine metabolism and serine and threonine metabolism; and small molecule metabolism including niacin and nicotinamide metabolism and PGI2 metabolism. Consistent with the findings on metabolic pathways, the main biological processes involved in rat IDD were energy metabolism [32], biological oxidation [33], and structural protein synthesis and decomposition [34]. Gly-Ser-Thr metabolic pathways are involved in biotransformation and metabolic activities during degeneration [35].…”

Comprehensive analysis of differences of N6-methyladenosine of lncRNAs between atrazine-induced and normal Xenopus laevis testis

“…Meanwhile, the changes of m 6 A modification of lncRNAs distribution were analyzed by exogenous stimulation. The profiles of m 6 A modification of lncRNAs in mammals were identified in recent years, such as mouse, rat and human [43][44][45][46]. Meanwhile, large intergenic noncoding RNAs (lincRNAs) which are one class of lncRNAs transcribed from intergenic regions are defined [47].. Key roles for lincRNAs in certain biological processes are starting to emerge.…”

Comprehensive Analysis of Differences of N6-Methyladenosine of Lncrnas Between Atrazine-Inducedand Normal Xenopus Laevis Testis

“…The pro les of m 6 A modi cation of lncRNAs in mammals were identi ed in recent years, such as mouse, rat and human [32][33][34][35]. Dominissini et al suggested that m 6 A in exonic regions was preferentially found in longer exons in human and mouse [36].…”