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

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.

N6-methyladenosine functions and its role in skin cancer.

N6-methyladenosine (m6A) methylation is the most abundant mammalian mRNA modification. m6A regulates RNA processing, splicing, nucleation, translation and stability by transferring, removing and recognizing m6A methylation sites, which are critical for cancer initiation, progression, metabolism and metastasis. m6A is involved in pathophysiological tumour development by altering m6A modification and expression levels in tumour oncogenes and suppressor genes. Skin cancers are by far the most common malignancies in humans, with well over a million cases diagnosed each year. Skin cancers are grouped into two main categories: melanoma and non-melanoma skin cancers (NMSC), based on cell origin and clinical behaviour. In this review, we summarize m6A methylation functions in different skin cancers, and discuss how m6A methylation is involved in disease development and progression. Moreover, we review potential prognostic biomarkers and molecular targets for early skin cancer diagnosis and treatment.

m6A modification of mRNA in skin diseases. / çš®è‚¤ç— ä¸­ç¼–ç RNA的m6A修饰.

N6-methyladenosine (m6A) is the predominant post-transcriptional modification for eukaryotic mRNA. It's regulated by methyltransferases, demethylases, and m6A binding proteins, and plays an important role in regulating splicing, translation, and degradation of mRNA. Skin diseases, especially immune skin diseases and skin tumors, have a complicated pathogenesis and are refractory to treatment, seriously affecting the patient quality of life. Recent studies have revealed that m6A and its regulatory proteins can affect the development of numerous skin diseases. The m6A modification was found to be involved in skin accessory development, including hair follicle and sweat gland formation. The level of m6A modification was significantly altered in a variety of skin diseases including melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and psoriasis, and affected a variety of biological processes including cell proliferation and differentiation migration. The m6A and its regulatory proteins may become potential molecular markers or therapeutic targets for skin diseases, and have promising clinical applications in early diagnosis, efficacy determination, prognosis prediction, and gene therapy of skin diseases.

Integrated analysis of tRNA-derived small RNAs reveals new therapeutic genes of hyperbaric oxygen in diabetic foot ulcers.

Background: To reveal the alterations of tRNA-derived small RNA (tsRNA) expression profiles induced by hyperbaric oxygen (HBO) treatment in diabetic foot ulcers (DFUs) and investigate new therapeutic targets. Materials & methods: tsRNA sequencing was employed in normal skin tissue, in DFUs, and after HBO treatment groups. A quantitative real-time PCR was used to validate tsRNA sequencing results and their targets levels. Bioinformatics analysis was performed to reveal their therapeutic functions in DFUs. Results: A total of 22 tsRNAs were differentially expressed in the three groups. Three selected tsRNAs were validated by quantitative real-time PCR for further analysis, which were all significantly overexpressed in DFU while being normally expressed after HBO treatment. Bioinformatics analysis disclosed that these tsRNAs may play therapeutic roles through the regulation of the Wnt signaling pathway. Conclusion: tsRNAs may be novel useful targets for HBO to treat DFUs.