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Identification of miR-190a-5p and miR-26b-5p as Potential microRNA Biomarkers for Psoriatic Arthritis
Omar F Cruz-Correa1, Darshini Ganatra1, Ameth N Garrido1
1Schroeder Arthritis Institute, University Health Network and Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Objective:
Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory arthritis that develops in 30% of patients with psoriasis, leading to increased morbidity and mortality and reduced quality of life. MicroRNAs (miRNAs) modulate gene expression and have been associated with the pathogenesis of immune-mediated disorders. We aimed to identify miRNAs that can be used as biomarkers for the development of PsA in patients with psoriasis.
Methods:
miRNA expression levels were assessed in serum samples from 28 patients with PsA, 35 patients with cutaneous psoriasis without arthritis (PsC), and 28 healthy controls through next-generation sequencing. Differential expression was assessed by linear modeling with empirical Bayes moderation corrected for sequencing batch, age, sex, and duration of psoriasis. For validation, we measured the expression of >191 genes predicted to be targeted by the dysregulated miRNAs using a custom NanoString probe panel in an independent cohort of 144 patients with PsA and 88 patients with PsC. The enrichment of specific pathways corresponding to the differentially expressed gene targets was examined using pathDIP.
Results:
In the discovery cohort, the miRNA miR-190a-5p was significantly down-regulated in patients with PsA compared to those with PsC (P< 0.05), and both miR-190a-5p and miR-26b-5p were down-regulated in patients with PsA versus healthy controls (P < 0.05). In the validation cohort, 26 gene targets of both of these miRNAs were differentially expressed. These genes were enriched in signaling pathways associated with bone formation and regeneration: Wnt and transforming growth factor β.
Conclusion:
Serum expression levels of miR-190a-5p and miR-26b-5p can potentially serve as biomarkers for PsA development.
Insights
Serum microRNAs miR-190a-5p and miR-26b-5p show potential as early biomarkers for psoriatic arthritis (PsA) development in psoriasis patients. These findings could aid in identifying individuals at risk for PsA.
Area of Science:
- Biomarkers
- Molecular Biology
- Immunology
Background:
- Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting psoriasis patients, leading to significant morbidity.
- MicroRNAs (miRNAs) play a role in immune-mediated diseases and may be involved in PsA pathogenesis.
Purpose of the Study:
- To identify microRNAs (miRNAs) that can serve as predictive biomarkers for psoriatic arthritis (PsA) development in patients with psoriasis.
- Investigate the role of specific miRNAs in the transition from psoriasis to psoriatic arthritis.
Main Methods:
- Serum miRNA expression was analyzed using next-generation sequencing in patients with PsA, psoriasis without arthritis (PsC), and healthy controls.
- Differential miRNA expression was validated using NanoString technology, and target gene enrichment analysis was performed.
- PathDIP was used to examine enrichment of signaling pathways related to differentially expressed gene targets.
Main Results:
- Down-regulation of miR-190a-5p was observed in PsA patients compared to PsC patients and healthy controls.
- miR-26b-5p was also down-regulated in PsA patients compared to healthy controls.
- Gene targets of these miRNAs were enriched in Wnt and transforming growth factor β signaling pathways, crucial for bone formation and regeneration.
Conclusions:
- Serum levels of miR-190a-5p and miR-26b-5p show promise as potential biomarkers for predicting psoriatic arthritis development.
- These miRNAs may offer insights into the molecular mechanisms underlying PsA pathogenesis.
- Further research could lead to early diagnostic tools for PsA.
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