Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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 Elbakkoush¹, Anas Khaleel², Chien-Tsai Liu¹

¹Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; ²Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang District, Taipei 11529, Taiwan.

For correspondence:- Chien-Tsai Liu Email: ctliu@tmu.edu.tw

Received: 17 January 2017 Accepted: 23 March 2017 Published: 29 April 2017

Citation: Elbakkoush AA, Khaleel A, Liu C. 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. Trop J Pharm Res 2017; 16(4):771-779 doi: 10.4314/tjpr.v16i4.5

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

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