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Updated: Dec 12, 2025
Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
IL6R is a target of miR-197 in human keratinocytes
Moamen Masalha1,2, Devorah Gur-Wahnon3, Tal Meningher1
1Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
Abstract:
Psoriasis is a chronic inflammatory disorder with cutaneous and systemic manifestations and substantial negative effects on patients' quality of life. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play a role in the pathogenesis of psoriasis. Previously studies, from others and by us, highlighted specific miRNAs that are dysregulated in psoriatic lesions. MicroRNA-197-3p (miR-197) expression is downregulated in psoriatic lesions compared to normal or uninvolved skin in patients with psoriasis. We have previously reported that miR-197 could modulate IL-22 and IL-17 signalling in psoriasis. Herein, we identify additional biochemical targets of miR-197 in psoriasis. We applied a transcriptome-wide biochemical approach, Protein argonaute-2 photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (Ago2 PAR-CLIP), to search for new targets of miR-197 in live keratinocytes, and validated its results using reporter assay and analysing by Western blot protein levels in cells overexpressing miR-197. Ago2 PAR-CLIP identified biochemical targets of miR-197, including the alpha subunit of the IL-6 receptor (IL6R). This work provides evidence that IL6R in bona-fide biochemical target of miR-197. IL6R is known to be up-regulated in psoriasis and even was considered as a possible therapeutic target. From the present data and our previous studies, it appears that miR-197 is a major regulator of the interaction between immune system cells and keratinocytes.
Insights
MicroRNA-197-3p (miR-197) is downregulated in psoriasis. This study identifies the IL-6 receptor (IL6R) as a new target of miR-197, suggesting miR-197 regulates immune cell and keratinocyte interactions in psoriasis.
Area of Science:
- Dermatology
- Molecular Biology
- Immunology
Background:
- Psoriasis is a chronic inflammatory skin disease impacting quality of life.
- MicroRNAs (miRNAs) are key regulators in psoriasis pathogenesis.
- MicroRNA-197-3p (miR-197) is downregulated in psoriatic lesions and modulates IL-17/IL-22 signaling.
Purpose of the Study:
- To identify novel biochemical targets of miR-197 in psoriasis.
- To investigate the role of miR-197 in regulating keratinocyte function.
- To further elucidate the molecular mechanisms underlying psoriasis.
Main Methods:
- Utilized Protein argonaute-2 photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (Ago2 PAR-CLIP) in keratinocytes.
- Applied transcriptome-wide analysis to identify miR-197 targets.
- Validated findings using reporter assays and Western blot analysis.
Main Results:
- Ago2 PAR-CLIP identified the alpha subunit of the IL-6 receptor (IL6R) as a direct biochemical target of miR-197.
- Confirmed IL6R is a bona fide target of miR-197.
- IL6R is known to be upregulated in psoriasis and is a potential therapeutic target.
Conclusions:
- miR-197 directly targets and regulates IL6R expression.
- miR-197 plays a significant role in the crosstalk between immune cells and keratinocytes in psoriasis.
- These findings highlight miR-197 as a potential therapeutic target for psoriasis.
