Abstract
Differences in expression of genes related to drug resistance and miRNAs regulating their expression in skin fibroblasts exposed to adalimumab and cyclosporine A
- Katowice School of Technology, The University of Science and Art, Katowice, Poland
- Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow Branch, Poland
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland
- Department of Cosmetology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland
Introduction
Adalimumab and cyclosporine A are drugs used in moderate to severe forms of psoriasis. Despite the molecular orientation of the drugs, there is a loss of adequate cell sensitivity to the anti-cytokine therapy.
Aim
To determine the changes in the gene expression profile associated with drug resistance in the culture of normal human dermal fibroblasts (NHDF) exposed to adalimumab or cyclosporine A compared to the controls.
Material and methods
NHDF was exposed to adalimumab/cyclosporine A for 2, 8, 24 h compared to the control culture. Molecular analysis was performed using mRNA and miRNA microarray techniques. The obtained results were analysed using PL – Grid infrastructure (p < 0.05).
Results
Of the 22277 ID mRNA, 47 are associated with drug resistance, of which the change in expression of 17 mRNA ID is statistically significant (p < 0.05). The greatest change in transcriptional activity (FC ≥ 1.3) was observed for GLO1, SLC10A3, TUFT1, STATH, ABCB1, AGTR1. Expression of these genes can be regulated by miR-199a-5p, miR-1231, miR-34a, miR-3188, and miR-106a (except AGTR1).
Conclusions
The analysis of changes in the expression of mRNA and miRNA related to drug resistance gives the possibility of monitoring the effectiveness of anti-cytokine therapy.
Keywords
psoriasis, drug resistance, personalized therapy, miRNA
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