Differences in expression of genes related to drug resistance and miRNAs regulating their expression in skin fibroblasts exposed to adalimumab and cyclosporine A

暴露于阿达木单抗和环孢素 A 的皮肤成纤维细胞中与药物耐药性相关的基因表达和调节其表达的 miRNA 的差异

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作者:Beniamin Grabarek, Piotr Schweizer, Iwona Adwent, Dominika Wcisło-Dziadecka, Jakub Krzaczyński, Celina Kruszniewska-Rajs, Joanna Gola

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

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.

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

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

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.

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