IL6R is a target of miR‐197 in human keratinocytes

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.