Identification of potential immune-related ceRNA Regulatory Network in UVB-irradiated human skin

Abstract

ABSTRACT For a better understanding the molecular biomarkers in UVB-induced skin damage, and its potential mechanism, we downloaded two microarray data sets on skin UVB damage from the Gene Expression Omnibus (GEO): GSE21429, GSE56754. By using the Limma package to analyze differential gene expression and co-expression network analysis to screen module genes, 16 common genes were identified (16 up-regulated). Gene Ontology analysis to explore the functional roles of these genes indicated that the common genes were associated mainly with melanin biosynthetic process and metabolic process. Gene Set Enrichment Analysis provided evidence that the most gene sets enriched in immune and inflammation-related signaling pathways in the UVB-treated subjects, as compared with the untreated subjects. The PPI network genes were ranked according to the degree of connectivity, the top three ranked genes: ”MLANA”, ”GPR143” and ”SFTPC” were identified as potential biomarkers using the area under the receiver operating characteristic curve. The relative proportion of 22 immune cell types was then calculated by using the CIBERSORT algorithm. A higher follicular helper T cell ratio in UVB-treated samples compared to untreated samples was observed. Moreover, three hub genes have also been shown to be associated with immune cells. Finally, through multiple online miRNA databases, we propose MLANA-miR-573-MALAT1/NEAT1, GPR143-miR-138-5p-MALAT1/ KCNQ1OT1 might be potential RNA regulatory pathways that control disease progression in UVB-induced skin damage. In summary, the present results provide novel insights into the UVB-radiation related biological process changes, and further offer a new clinical application for prognosis and diagnostic prediction of UVB radiation-mediated skin damage.