Severe Burn Injury Significantly Alters the Gene Expression and m6A Methylation Tagging of mRNAs and lncRNAs in Human Skin

Abstract

N6-methyladenosine (m6A) modulates RNA metabolism and functions in cell differentiation, tissue development, and immune response. After acute burns, skin wounds are highly susceptible to infection and poor healing. However, our understanding of the effect of burn injuries on m6A methylation and their potential mechanism is still limited. Human m6A-mRNA&lncRNA Epitranscriptomic microarray was used to obtain comprehensive mRNA and lncRNA transcriptome m6A profiling and gene expression patterns after burn injuries in human skin tissue. Bioinformatic and functional analyses were conducted to find molecular functions. Microarray profiling showed that 65 mRNAs and 39 lncRNAs were significantly hypermethylated; 5492 mRNAs and 754 lncRNAs were significantly hypomethylated. Notably, 3989 hypomethylated mRNAs were down-expressed and inhibited many wound healing biological processes and pathways including in the protein catabolic process and supramolecular fiber organization pathway; 39 hypermethylated mRNAs were up-expressed and influenced the cell surface receptor signaling pathway and inflammatory response. Moreover, we validated that m6A regulators (METTL14, METTL16, ALKBH5, FMR1, and HNRNPC) were significantly downregulated after burn injury which may be responsible for the alteration of m6A modification and gene expression. In summary, we found that homeostasis in the skin was disrupted and m6A modification may be a potential mechanism affecting trauma infection and wound healing.