Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients

Liu,Qingxiu; Cui,Feiyi; Wang,Menglei; Xiong,Hao; Peng,Xiaoming; Liang,Liuping; Li,Li; Zhang,Jing; Peng,Xuebiao; Zeng,Kang

doi:10.3892/mmr.2018.8934

Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients

Authors:
- Qingxiu Liu
- Feiyi Cui
- Menglei Wang
- Hao Xiong
- Xiaoming Peng
- Liuping Liang
- Li Li
- Jing Zhang
- Xuebiao Peng
- Kang Zeng
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Affiliations: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Medical Apparatus and Equipment Deployment, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: April 26, 2018 https://doi.org/10.3892/mmr.2018.8934
Pages: 550-556

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Abstract

Expression of microRNA-338-3p (miR-338-3p) was aberrantly elevated in pemphigus vulgaris (PV), although its role in PV is still unknown. The present study investigated the functional role and possible molecular mechanisms of miR-338-3p in PV. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-338-3p expression in peripheral blood mononuclear cells (PBMCs) from patients with PV. Correlation with disease severity and anti-desmoglein 3 antibody (anti-Dsg3) titers were analyzed in patients with PV. The effects of overexpression and knockdown of miR-338-3p expression in PBMCs and effects on Th1 and Th2 cytokines were also examined using ELISA. The luciferase reporter analysis, RT-qPCR and western blot analysis were applied to investigate potential and functional target genes. The data showed that miR-338-3p expression was significantly upregulated in PV and the upregulation of miR-338-3p associated with disease severity and a high anti-Dsg3 antibody titer. Expression of miR-338-3p/mimic in healthy PBMCs significantly downregulated Th1 cytokine (IFN-γ) and upregulated Th2 cytokines (IL-4 and IL-10), whereas knockdown of miR-338-3p expression in PBMCs from patients with PV induced the reverse effects. Overexpression of miR-338-3p suppressed cell viability. Luciferase reporter, RT-qPCR and western blot assays idnicated that TNFR1-associated death domain protein (TRADD) was the direct and functional target of miR-338-3p. Increased expression of miR-338-3p contributed to the production of Dsg3 antibody by inhibiting TRADD expression to induce an imbalance in Th1/Th2 cell functions. Taken together, this study suggests that miR-338-3p may be used as a potential therapeutic target for PV treatment.

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