The overexpression of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has the potential to significantly reduce inflammatory cytokine levels by the mechanism in which MEG3 interacts with microRNA (miR)-146a, according to study results published in Molecular and Cellular Biochemistry.
Investigators of this study sought to explore the role and mechanism of lncRNA MEG3 in the inflammatory response of ankylosing spondylitis (AS) and the relationship between MEG3 or miR-146a and inflammatory cytokines.
The study included data of 33 patients with AS and 16 healthy control participants; researchers collected blood samples from all participants and extracted human fibroblast-like synovial cells from AS samples for in vitro experiments. They used enzyme-linked immunosorbent assay kits to detect the levels of inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Investigators also performed quantitative real-time polymerase chain reaction to measure the expression of MEG3, miR-146a, and inflammatory cytokines. They used dual-luciferase reporter and RNA immunoprecipitation assay kits to evaluate the interaction between MEG3 and miR-146a and then used Pearson analysis to determine correlations between MEG3 or miR-146a and inflammatory cytokines.
In enzyme-linked immunosorbent assay kits results, IL-1β, IL-6, and TNF-α levels all significantly increased among patients with AS compared with control participants, and quantitative real-time polymerase chain reaction revealed significantly lower MEG3 levels in the AS vs control group. Downregulation of MEG3 in AS resulted in the increased expression of inflammatory cytokines. When testing the influence of MEG3 on the inflammatory response, upregulation of MEG3 suppressed the inflammatory response, and the silenced MEG3 promoted an increase of inflammatory cytokines. Expression of miR-146a positively correlated with IL-1β, IL-6, and TNF-α levels. Investigators found that upregulated miR-146a could directly interact with MEG3 — overexpression of MEG3 blocked the expression of miR-146a, and miR-146a expression increased after MEG3 was knocked down. Therefore, the anti-inflammatory effect of MEG3 in patients with AS could be achieved by suppression of miR-146a expression.
A study limitation included the small number of samples. Future studies should confirm these findings in a larger sample size.
Investigators suggested that MEG3 is an important biomarker for AS in which MEG3 may be targeted to regulate the inflammatory response by suppressing the expression of miR-146a. This mechanism could be used as a biomarker for AS, which could provide a potential new means for targeted treatment.
Li Y, Zhang S, Zhang C, Wang M. LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a [published online January 1, 2020]. Mol Cell Biochem. doi:10.1007/s11010-019-03681-x