Potential molecular characteristics in situ in response to repetitive UVB irradiation.

Wenqi Chen,Jinhai Zhang

doi:10.1186/s13000-016-0579-y

Abstract

BackgroundTo identify molecular characteristics in situ in response to repetitive UVB (ultraviolet-B) irradiation.MethodsMicroarray data from the Gene Expression Omnibus were re-analyzed to identify DEGs (differentially expressed genes) between UVB-irradiated and non-irradiated skin biopsies. Enrichment and annotation analyses were performed respectively using DAVID, and TSGene and TAG databases. PPIs (protein-protein interactions) were analyzed using STRING, and miRNAs (microRNAs) and TFs (transcription factors) were predicted separately by miRNA-related databases and ENCODE. Accordingly, the PPI network and regulatory networks were visualized using Cytoscape, and they were merged together to obtain an integrated network for mining densely connected modules.ResultsAltogether, 151 up- and 64 down-regulated genes were identified between UVB-irradiated and non-irradiated skin biopsies, among which down-regulated DNAJB4 and SLIT2 were annotated as tumor-suppressors and up-regulated KIT was annotated as an oncogene. The up-regulated DEGs were significantly enriched in biological processes related to pigmentation (DCT, SOX10, TYRP1, TYR, MLPH, KIT and GPR143), while the down-regulated DEGs were dramatically related to haemopoiesis and the immune system (GPR183, INHBA, PTPRC, PLEK, CD8A and IKZF1). Furthermore, many miRNAs were screened for the DEGs, including miR-206 and miR-496 targeting KIT, miR-184 targeting DCT, and highly significant miR-337-5p, miR-21 and miR-16. Additionally, TFs were identified for the DEGs, among which PAX5 and HNF4A targeted MLPH and GPR143, respectively, while BATF, SPI1 and EP300 jointly target GPR183, PTPRC and PLEK.ConclusionsThe pigmentation and immune system implicated by DEGs, miRNAs and TFs might be important molecular mechanisms in response to UVB irradiation.

Highlights

To identify molecular characteristics in situ in response to repetitive UVB irradiation
The pigmentation and immune system implicated by Differentially expressed genes (DEGs), miRNAs and Transcription factors (TFs) might be important molecular mechanisms in response to UVB irradiation
Expressed genes With cutoffs of P-value < 0.05 and |log2 fold change (FC)| >0.5, altogether 215 DEGs including 151 up- and 64 down-regulated genes were identified in UVB-irradiated skin biopsies compared with non-irradiated controls

Summary

Methods

This article does not contain any studies with human participants or animals performed by any of the authors. A gene expression matrix was obtained and subsequently subjected to differential expression analysis between UVB-irradiated and non-irradiated skin biopsies using the t-test. Integrated network construction and module screening The PPI network and the two regulatory networks were further merged together to obtain one integrated network among TFs, miRNAs and DEGs. Subsequently, the integrated network was mined to screen out densely connected modules with default cutoffs (degree cutoff: 2, node score cutoff: 0.2, K-core: 2, and maximum depth: 100) using MCODE v1.31 (Molecular Complex Detection, http://baderlab.org/Software/MCODE) [26]. Functional enrichment analyses were performed for the densely connected modules to identify their biological relevance using DAVID v6.7

Results

Conclusions

Background

Conclusion