Characterization of MicroRNA and Gene Expression Profiles Following Ricin Intoxication

Abstract

Ricin, derived from the castor bean plant, is a highly potent toxin, classified as a potential bioterror agent. Current methods for early detection of ricin poisoning are limited in selectivity. MicroRNAs (miRNAs), which are naturally occurring, negative gene expression regulators, are known for their tissue specific pattern of expression and their stability in tissues and blood. While various approaches for ricin detection have been investigated, miRNAs remain underexplored. We evaluated the effect of pulmonary exposure to ricin on miRNA expression profiles in mouse lungs and peripheral blood mononuclear cells (PBMCs). Significant changes in lung tissue miRNA expression levels were detected following ricin intoxication, specifically regarding miRNAs known to be involved in innate immunity pathways. Transcriptome analysis of the same lung tissues revealed activation of several immune regulation pathways and immune cell recruitment. Our work contributes to the understanding of the role of miRNAs and gene expression in ricin intoxication.

Introduction to the Toxins Special Issue “Ricin Toxins”

“…They show significant changes in the lung tissue expression levels of miRNAs involved in innate immunity pathways. They confirm these findings by gene expression analysis and show activation of immune regulation pathways and immune cell recruitment after ricin exposure [12]. Sousa et al [13] describe an accelerated solvent extraction (ASE) method followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and MALDI-TOF-MS/MS for extraction and detection of ricin in forensic samples.…”

“…Micro RNA (miRNA) profiles can help understand ricin toxicity mechanisms and could serve as potential biomarkers for ricin intoxication. Pillar et al [12] investigate the effect of pulmonary exposure of mice to ricin on miRNA expression profiles in mouse lungs. They show significant changes in the lung tissue expression levels of miRNAs involved in innate immunity pathways.…”

MicroRNAs in ascending thoracic aortic aneurysms

“…All statistical analysis was conducted using R software version 3.2. NanoString data pre-processing and normalization followed by differential expression analysis was performed using DEseq2 package [27] and in-house scripts [28] identifying the mean values from the patients' samples. The mean value of negative controls was set as the lower threshold for each sample; only miRNAs with at least 50% of their values above the lower threshold were included in the analysis.…”

“…The false discovery rate method was used to control multiple observations, and the adjusted P-value was used for further analysis. Fold-change difference were calculated for each comparison and the P-value was determined where P-value <0.05 was considered significant [28][29][30]. The miRNAs which showed significant expression level differences between BB and BA samples were selected for further investigation.…”

Combined analyses of RNA-sequence and Hi-C along with GWAS loci—A novel approach to dissect keloid disorder genetic mechanism

“…MiRTarBase is a comprehensive database of experimentally verified miRNA-target interactions, which were verified either by highly reliable methods such as WB, fluorescence reporter experiments, RT-qPCR or predicted by high-throughput experiments like photoactivatable ribonucleoside enhanced crosslinking, immunoprecipitation and crosslinking immunoprecipitation coupled with high throughput sequencing [ 55 ]. Therefore, it was used to explore the functions of DEmiRNAs.…”