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

Abdallah Ahmed Elbakkoush, Anas Khaleel, Chien Tsai Liu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)771-779
Number of pages9
JournalTropical Journal of Pharmaceutical Research
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • Biomarkers
  • Granulysin
  • MicroRNA signature
  • Severe cutaneous adverse drug reactions (SCAR) Steven-Johnson Syndrome
  • Toxic epidermal necrolysis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology (medical)

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