IL6R is a target of miR-197 in human keratinocytes.


Journal

Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549

Informations de publication

Date de publication:
08 2021
Historique:
revised: 04 08 2020
received: 25 03 2020
accepted: 06 08 2020
pubmed: 12 8 2020
medline: 31 3 2022
entrez: 12 8 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32780449
doi: 10.1111/exd.14169
doi:

Substances chimiques

IL6R protein, human 0
MIRN197 microRNA, human 0
MicroRNAs 0
Receptors, Interleukin-6 0
Cathepsins EC 3.4.-
Cysteine Endopeptidases EC 3.4.22.-
CTSV protein, human EC 3.4.22.43

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1177-1186

Informations de copyright

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Moamen Masalha (M)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Devorah Gur-Wahnon (D)

Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Tal Meningher (T)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.

Iddo Z Ben-Dov (IZ)

Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Riad Kassem (R)

Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel.

Yechezkel Sidi (Y)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Dror Avni (D)

Laboratory of Molecular Cell Biology, Center for Cancer Research and Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.

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