IL6R is a target of miR-197 in human keratinocytes

Moamen Masalha, Devorah Gur-Wahnon, Tal Meningher, Iddo Z. Ben-Dov, Riad Kassem, Yechezkel Sidi*, Dror Avni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1177-1186
Number of pages10
JournalExperimental Dermatology
Volume30
Issue number8
DOIs
StatePublished - Aug 2021

Funding

FundersFunder number
Meir and Edith Rosenfeld Foundation
Israel Cancer Association20110076, 20160038
Tel Aviv University
Council for Higher Education

    Keywords

    • IL6R
    • PAR-CLIP
    • keratinocytes
    • miR-197
    • psoriasis

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