<i>IL6R</i> is a target of miR‐197 in human keratinocytes

Masalha, Moamen; Gur‐Wahnon, Devorah; Meningher, Talal; Ben‐Dov, Iddoddo.Z; Kassem, Riad; Sidi, Yechezkel; Avni, Dror

doi:10.1111/exd.14169

Cited by 8 publications

(5 citation statements)

References 68 publications

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“…MiRNAs are widely found in many species, and their application in genomics provides many therapeutic advantages for gene regulation of psoriasis. Differentially expressed miRNAs may be involved in the pathogenesis of psoriasis through mediating cell proliferation, inflammation, and immunity via regulating the levels of downstream target genes and signaling pathways [26, 27]. In this study, we further investigated the mechanism of XIST/miR-338-5p in psoriasis.…”

Section: Discussion/conclusionmentioning

confidence: 99%

LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation

Wang¹,

Jiang

Chen

et al. 2022

Skin Pharmacol Physiol

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Introduction: Psoriasis is an immune-mediated polygenic inflammatory skin disease, keratinocyte proliferation is an important mechanism. The study investigated the role and regulatory relationship between lncRNA XIST and miR-338-5p in psoriatic patients and cell models. Methods: Serum samples were collected from 55 psoriasis patients. HaCaT was recruited for the cell experiments, and induced by M5 cytokines to mimic psoriasis in vitro. XIST and miR-338-5p levels were detected via qRT-PCR. Cell viability under different treatments was evaluated using CCK-8. ELISA was applied to measure the concentration of inflammatory cytokines. The regulatory relationship was confirmed using luciferase reporter gene assay. Results: Serum XIST was elevated in patients with psoriasis, and can distinguish the psoriasis patients from healthy controls according to the ROC curve. High level of XIST was positively correlated with with PASI score and serum TNF-α, IL-17A and IL-22 concentrations in psoriasis patients. XIST silencing suppressed M5-induced keratinocyte proliferation and restrained the discharge of inflammatory cytokines (TNF-α, IL-17A, IL-22) and chemokines (CXCL1, CXCL8, CCL20). XIST can sponge miR-338-5p, and miR-338-5p downregulation abolished the inhibitory effect of XIST silencing on cell proliferation and inflammation. miR-338-5p was at high expression in the clinical serum samples from psoriasis patients. The target relationship between miR-338-5p and IL-6 was proved. Conclusion: LncRNA XIST is highly expressed in the serum of patients with psoriasis, and was positively correlated with disease severity and inflammation. XIST may regulate keratinocyte proliferation and inflammation via regulating miR-338-5p/IL-6 axis.

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Section: Discussion/conclusionmentioning

confidence: 99%

LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation

Wang¹,

Jiang

Chen

et al. 2022

Skin Pharmacol Physiol

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“…The assay was performed on SCL-II cells. Cells were grown in the presence of 100 μM 4-thiouridine (4SU) for 24 h and processed as described in Masalha et al [ 60 ]. Ago2 PAR-CLIP data were deposited in NCBI’s Gene Expression Omnibus, GEO accession number GSE155538.…”

Section: Methodsmentioning

confidence: 99%

MiR-199a-3p Induces Mesenchymal to Epithelial Transition of Keratinocytes by Targeting RAP2B

Masalha

Meningher

Mizrahi

et al. 2022

IJMS

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Cutaneous squamous cell carcinoma (CSCC) is an epidermal skin cancer that evolves from normal epidermis along several pre-malignant stages. Previously we found specific miRNAs alterations in each step along these stages. miR-199a-3p expression decreases at the transition to later stages. A crucial step for epithelial carcinoma cells to acquire invasive capacity is the disruption of cell–cell contacts and the gain of mesenchymal motile phenotype, a process known as epithelial-to-mesenchymal transition (EMT). This study aims to study the role of decreased expression of miR-199a-3p in keratinocytes’ EMT towards carcinogenesis. First, we measured miR-199a-3p in different stages of epidermal carcinogenesis. Then, we applied Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) assay to search for possible biochemical targets of miR-199a-3p and verified that Ras-associated protein B2 (RAP2B) is a bona-fide target of miR-199a-3p. Next, we analyzed RAP2B expression, in CSCC biopsies. Last, we evaluated possible mechanisms leading to decreased miR-199a-3p expression. miR-199a-3p induces a mesenchymal to epithelial transition (MET) in CSSC cells. Many of the under-expressed genes in CSCC overexpressing miR-199a-3p, are possible targets of miR-199a-3p and play roles in EMT. RAP2B is a biochemical target of miR-199a-3p. Overexpression of miR-199a-3p in CSCC results in decreased phosphorylated focal adhesion kinase (FAK). In addition, inhibiting FAK phosphorylation inhibits EMT marker genes’ expression. In addition, we proved that DNA methylation is part of the mechanism by which miR-199a-3p expression is inhibited. However, it is not by the methylation of miR-199a putative promoter. These findings suggest that miR-199a-3p inhibits the EMT process by targeting RAP2B. Inhibitors of RAP2B or FAK may be effective therapeutic agents for CSCC.

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“…Simondurairaj et al reported an increase in IL-6R expression in gastric cancer, indicating that IL-6R may be both a therapeutic target and a prognostic marker of gastric cancer [35]. Overexpression of both IL-6 and IL-6R has been observed in patients with psoriasis [36,37]. It is therefore possible that blocking the action of TNF-a by adalimumab affects only the expression of IL-6, not its receptor IL-6R.…”

Section: Nevertheless Biesemann Et Al Demonstrated In Anmentioning

confidence: 99%

Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A

Buda,

Michalski,

Warmusz

et al. 2023

pdia

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Introduction:The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. Material and methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 μg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 μg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques. Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96). Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.

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IL6R is a target of miR‐197 in human keratinocytes

Cited by 8 publications

References 68 publications

LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation

LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation

MiR-199a-3p Induces Mesenchymal to Epithelial Transition of Keratinocytes by Targeting RAP2B

Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A

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