MicroRNA and gene signature of severe cutaneous drug hypersensitivity reactions reveal the role of miR-483- 5p/miR-28-5p in inflammation by targeting Granulysin gene
Purpose: To build a microRNA and gene signature of severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Methods: MicroRNA expression profiles were downloaded from miRNA expression profile of patients’ skin suffering from TEN using an array comprising of 372 miRNAs; download site: www.jacionline.org. The patient samples were eight TEN, ten SJS patients and twenty-two healthy individuals. A total of 192 microRNAs were found with unique expression patterns (overexpressed) in contrast with healthy skin controls and patients. Thereafter, the following databases were used for downstream analysis: geneMANIA, DIANA-miRPath version 3, DIANA-TarBase version 7.0, Ingenuity Pathway Analysis (IPA) as well as DAVID, STRING and GENECODIS online tools.
Results: Granulysin (GNLY) geneMANIA database search yielded 21 interacting genes that were 64.6 % in physical interaction, 17 % in co-expression pattern. miRBD potential microRNAs that target the 21 genes were 79 miRs. Eighteen miRs overlap between the overexpressed miRs from SJS/TEN samples and the miRs targeting the 21 genes. Moreover, Ingenuity pathway analysis IPA revealed that the microRNAs were involved in inflammation.
Conclusion: Analysis of differential microRNA expressions reveals two significant DE miRs that target Granulysin (483-5p/miR-28-5p). MiR-GNLY loop interactions in hypersensitivity reactions may function as biomarkers for SCAR including SJS and TEN.
Keywords: Severe cutaneous adverse drug reactions (SCAR) Steven-Johnson Syndrome, Toxic epidermal necrolysis, Granulysin, Biomarkers, MicroRNA signature