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Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy
1Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Background:
MicroRNAs (miRNAs) are endogenous, nonprotein-coding, regulatory RNAs with important roles in health and disease. miRNAs are present in the circulation in a stable form and their levels are altered in diseases.
Objectives:
To determine whether antitumour necrosis factor (TNF)-α therapy affects serum miRNA levels in patients with psoriasis.
Methods:
Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. miRNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti-TNF-α-regulated miRNAs in patients' sera. The expression of five miRNAs regulated by etanercept was measured by quantitative polymerase chain reaction (qPCR) in sera from patients and controls.
Results:
Etanercept significantly suppressed a panel of 38 miRNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by qPCR showed that serum levels of miR-106b, miR-26b, miR-142-3p, miR-223 and miR-126 were significantly downregulated by etanercept in responders (Psoriasis Area and Severity Index change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not upregulated in patients with psoriasis compared with healthy controls. The level of four circulating miRNAs was significantly different (increased: miR-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum.
Conclusions:
The level of circulating miRNAs is altered in psoriasis. Anti-TNF-α therapy has a profound effect on the serum level of miRNAs; however, these are not related to disease severity. Our results suggest that changes in the miRNA level may reflect a previously unknown effect of anti-TNF-α therapy. Our results suggest the involvement of miRNAs in pathways affected by anti-TNF-α therapy and warrant further investigation of serum miRNAs as potential biomarkers for therapy response in psoriasis.
Insights
Anti-tumour necrosis factor-alpha (TNF-α) therapy significantly alters serum microRNA (miRNA) levels in psoriasis patients. These changes suggest a novel therapeutic effect and potential for miRNA biomarkers in treatment response.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are regulatory RNAs crucial in biological processes.
- Circulating miRNAs are stable and their levels change in disease states.
Purpose of the Study:
- To investigate the impact of anti-tumour necrosis factor-alpha (TNF-α) therapy on serum miRNA levels in psoriasis patients.
- To identify specific miRNAs affected by etanercept treatment.
Main Methods:
- Serum samples from psoriasis patients and healthy controls were analyzed.
- miRNA expression profiling identified differentially expressed miRNAs.
- Quantitative polymerase chain reaction (qPCR) validated changes in specific miRNAs after etanercept or methotrexate treatment.
Main Results:
- Etanercept downregulated a panel of 38 immune-cell derived miRNAs, implicated in inflammation and autoimmunity.
- qPCR confirmed downregulation of miR-106b, miR-26b, miR-142-3p, miR-223, and miR-126 in etanercept responders.
- Methotrexate did not significantly alter these miRNA levels. Four circulating miRNAs differed between psoriasis patients and healthy controls.
Conclusions:
- Psoriasis is associated with altered circulating miRNA levels.
- Anti-TNF-α therapy profoundly affects serum miRNA profiles, suggesting a new therapeutic mechanism.
- Investigating serum miRNAs may reveal biomarkers for predicting anti-TNF-α therapy response in psoriasis.
