MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumatoid arthritis in an association with the REST/mTOR axis.

Abstract

BACKGROUND:

It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression.

METHODS:

Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for in vivo experiments.

RESULTS:

miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our in vivo study.

CONCLUSION:

This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.

• Authors: Wei Sun, Yijun Zhang, Guanghui Wang
• Journal: Molecular pain (Mol Pain) 2021 Jan-Dec Vol. 17 Pg. 17448069211041847 ISSN: 1744-8069 [Electronic] United States
• PMID: 34433333 (Publication Type: Journal Article)

Chemical References

• MIRN137 microRNA, human
• MIRN137 microRNA, rat
• MicroRNAs
• Lysine

Topics

• Adult
• Animals
• Arthritis, Rheumatoid (genetics, metabolism, pathology)
• Female
• Fibroblasts (metabolism)
• Humans
• Inflammation (pathology)
• Lysine (genetics, metabolism)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Rats, Wistar
• Synoviocytes (metabolism)
• Rats