MicroRNA Microarray-Based Identification of Involvement of miR-155 and miR-19a in Development of Oral Lichen Planus (OLP) by Modulating Th1/Th2 Balance via Targeting eNOS and Toll-Like Receptor 2 (TLR2)

Liang Wang, Wei Wu, Jijun Chen, Youhua Li, Ming Xu, Yawei Cai

Journal:MEDICAL SCIENCE MONITOR

IF:1.89

DOI:10.12659/MSM.907497

PMID:

Published:2018-05-29

research field:分子生物学皮肤病学口腔病理学免疫学

Abstract

Background A wide range of microRNAs (miRNAs) have been shown to play a significant role in disease regulation. The objective of this study was to explore the role of miR-155 and miR-19a in the regulation of oral lichen planus (OLP). Material/Methods Microarray assay, real-time PCR, Western blot assay, computational analysis, luciferase assay, ELISA, and immunohistochemistry analysis were carried out to investigate the role of miR-155 and miR-19a in OLP. Results According to microarray assay and real-time PCR results, the expression of miR-155 was most significantly decreased among the 16 candidate miRNAs in the OLP group, whereas the expression of miR-19a was most significantly increased. MiR-155 and miR-19a directly targeted endothelial nitric oxide synthase (eNOS) and TLR2, respectively, since only the cells co-transfected with miR-155/wild-type eNOS 3′UTR or cells co-transfected with miR-19a/wild-type TLR2 3′UTR exhibited decreased luciferase activity. In addition, the expression of TLR2 was highly upregulated in OLP, whereas the expression of eNOS was significantly downregulated. A negative correlation was found between miR-19a and TLR2 mRNA, with a coefficient value of −0.40. Similarly, a negative correlation was found between miR-155 and eNOS mRNA, with a coefficient value of −0.54. A lower level of NO, IL-4, IL-5, and IL-10 was observed in OLP, which was also accompanied by a higher level of TNF-α and IFN-γ. Finally, the upregulation in miR-155 directly decreased the expression of eNOS and further inhibited the production of NO. Downregulation of miR-19a directly increased the expression of TLR2. The inhibition of NO production and the enhancement in TLR2 expression synergistically increased the production of TNF-α and IFN-γ, while decreasing the levels of IL-4, IL-5, and IL-10.

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