Circulating microRNA profile unveils mechanisms of action of acitretin for psoriasis vulgaris

ABSTRACT

Psoriasis vulgaris is a common chronic and recurrent inflammatory skin disease. In clinical practice, acitretin is the first-line treatment drug for psoriasis vulgaris. MicroRNAs (miRNAs) play a vital role in the initiation and development of psoriasis vulgaris. However few studies focused on the mechanisms of acitretin in the treatment of psoriasis vulgaris from the perspective of miRNAs. Here, the expression profiles of circulating miRNAs in the plasma of 12 patients with psoriasis vulgaris before and after acitretin treatment were sequenced. Three miRNAs (miR-146a-5p, miR-122-5p and miR-21-5p) were identified using expression pattern analysis, and the levels were significantly decreased after acitretin treatment (P< 0.001). Receiver operating characteristic (ROC) analyses indicated that the three miRNAs have the potential to be utilized as molecular markers to evaluate the therapeutic effect of acitretin, and the values of the area under the curve (AUC) were 0.825, 0.831, and 0.796, respectively. In addition, we predicted target genes of the three miRNAs and performed signaling pathway enrichment analyses. The results demonstrated that the target genes were mainly involved in the MAPK, JAK-STAT, and NF-κB signaling pathways, which were further validated through in vitro experiments. In conclusion, acitretin can suppress miRNA-mediated MAPK, JAK-STAT, and NF-κB signaling pathways by decreasing miRNAs expression, thereby inhibiting the proliferation and inflammatory response of keratinocytes.

GRAPHICAL ABSTRACT

KEYWORDS:

• Psoriasis vulgaris
• acitretin
• miRNA
• MAPK
• JAK-STAT
• NF-ΚB

Highlights

• Three miRNAs were significantly decreased after acitretin treatment

• Targets of the miRNAs involved in MAPK, JAK-STAT, and NF-κB signaling pathways

• Acitretin can suppress miRNA-mediated signaling pathways by decreasing miRNAs

• Three miRNAs can be utilized to evaluate the therapeutic effect of acitretin

Acknowledgements

We thank Junwei Wang, Xueping Jia, Zhifeng Qi, Hongxin Jiao, Jinlong Shi, Yuanyuan Yang, Shuoting Li, Yanan Jiang, Jufeng Li, Xiaoxiao Yang, and Zhangchen Jiang for collecting the clinical samples.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Luoyang Medical and Health Science and Technology Plan Project of Henan Province (No. 1717001A);Luoyang Medical and Health Science and Technology Plan Project of Henan Province [1717001A].