MiR‐885‐3p is down‐regulated in peripheral blood mononuclear cells from T1D patients and regulates the inflammatory response via targeting TLR4/NF‐κB signaling

Abstract

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive destruction of insulin-production pancreatic β cells. Recently, microRNAs (miRNAs) have emerged as important regulators in T1D. The present study aimed to determine miR-885-3p expression in T1D patients and to examine the effects of miR-885-3p on the inflammatory response in human monocytes.Methods: Relevant gene expression levels were determined by a quantitative polymerase chain reaction; western blotting and enzyme-linked immunosorbent assays determined the respective protein levels; and the interaction between miRNA and the downstream targets was evaluated using a luciferase reporter assay.Results: MiR-885-3p is down-regulated and the levels of pro-inflammatory cytokines are increased in peripheral blood mononuclear cells (PBMCs) from T1D patients compared to healthy controls. MiR-885-3p overexpression suppressed mRNA expression and secreted protein levels of pro-inflammatory cytokines in THP-1. A luciferase reporter assay showed that miR-885-3p directly targeted the 3'untranslated region of Toll-like receptor 4 (TLR4) and miR-885-3p overexpression down-regulated TLR4 expression in THP-1 cells. The TLR4 mRNA expression level was increased in PBMCs isolated from T1D patients compared to heathy controls.TLR4 overexpression increased the secretion of pro-inflammatory cytokines and enhanced the activity of NF-κB signaling, and also attenuated the inhibitory effects of miR-885-3p overexpression on pro-inflammatory cytokine secretion and the activity of NF-κB signaling in THP-1 cells. Conclusions:The present study identified the down-regulation of miR-885-3p and up-regulation of TLR4 in PBMCs isolated from T1D patients. Further mechanistic data demonstrated that miR-885-3p overexpression represses the production of proinflammatory cytokines via targeting TLR4/NF-κB signaling in THP-1 cells.

Untargeted sequencing of circulating microRNAs in a healthy and diseased older population

“…Previous studies showed that miR-885-3p, miR-505-3p and miR-194-5p are principally involved in immune responses. Overexpression of miR-885-3p repressed the pro-inflammatory cytokine production 38 . Up- and/or down-regulation of miR-505-3p and miR-194-5p seem to regulate the transcription of key genes that mediate inflammatory responses 39 , 40 .…”

RNA-seq Identifies circRNAs Expression Profiles and Potential Biomarkers for Intracerebral Hemorrhage

“…Of these, miR-663b was reported to be increased in acute myocardial infarction [51,52] and ischemic heart disease [53], and the miR-671 expression level was reported to affect brain function [54]. MiR-885-3p is downregulated in monocular cells and regulates the in ammatory response by targeting TLR4/NF-kB signaling [55]. MiR296-5p is involved in NRG1/ERBB2/ERBB3 signaling and suppresses EMT in hepatocellular carcinoma [56].…”

Role of microRNAs in Pressure Ulcer Immune Response, Pathogenesis, and Treatment

“…In patients with type-1 diabetes, miR-885-3p is downregulated and there is upregulation of pro-inflammatory cytokine expression by peripheral blood mononuclear cells. MiR-885-3p overexpression can result in a decrease in NFκB activity within these cells through inhibition of toll-like receptor (TLR)-4 [102]. Vitamin D has been shown to lower hypoxia-induced activation of NFκB and ROS production in cerebral endothelial cells [103].…”