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Δευτέρα 31 Μαΐου 2021

miR-489-3p inhibits TLR4/NF-κB signaling to prevent inflammation in psoriasis

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Exp Ther Med. 2021 Jul;22(1):744. doi: 10.3892/etm.2021.10176. Epub 2021 May 11.

ABSTRACT

Psoriasis is a chronic inflammatory skin disease whose etiology has not yet been determined. MicroRNAs (miRs) regulate the early stages of psoriasis and are targets for therapeutic intervention. The present study aimed to investigate the functional role of miR-489-3p in psoriasis. The present study first assessed the expression levels of miR-489-3p and Toll-like receptor (TLR)4 mRNA using reverse transcription-quantitative PCR, and also detected the protein expression levels of TLR4 and NF-κB via western blot analysis. TargetScan and miRDB target gene prediction tools were used to confirm the regulation of Toll-like receptor (TLR)4 by miR-489-3p. Moreover, a Cell Counting Kit (CCK)-8 assay was conducted to evaluate cell viability, while cell cycle and colony formation assays were performed to evaluate cell proliferation. Human keratinocytes (HaCa T) were co-transfected with TLR4-small interfering RNA and miR-489-3p-inhibitor plasmids, and analysis of cell proliferation and inflammatory cytokine secretion was performed using CCK-8 assay and ELISA. It was found that miR-489-3p expression was downregulated in patients with psoriasis. Bioinformatics analysis identified that TLR4 was a direct target of miR-489-3p. This was confirmed via luciferase reporter assays in HaCaT cells. The overexpression of miR-489-3p inhibited the TLR4/NF-κB signaling pathway and reduced cell proliferation. TLR4 silencing alleviated the effects of miR-489-3p, and enhanced cell proliferation and inflammatory cytokine secretion. Taken together, these data suggested that miR-489-3p may be a key effector of psoriasis, which promotes inflammatory responses by direct targeting of TLR4. miR-489-3p therefore represents a promising prognostic biomarker and therapeutic target for psoriasis treatment.

PMID:34055060 | PMC:PMC8138277 | DOI:10.3892/etm.2021.10176

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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