MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care

Abstract

Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids. Based on that microRNA expression for serum samples of sulfur mustard patients were examined, to establish specific microRNA patterns as a basis for diagnostic use and insight into affected molecular pathways. Patients were categorized based on their long-term complications into three groups and microRNA serum levels were measured. The differentially regulated microRNAs and their corresponding gene targets were identified. Cell cycle arrest, ageing and TGF-beta signaling pathways showed up to be the most deregulated pathways. The candidate microRNA miR-143-3p could be validated on all individual patients. In a ROC analysis miR-143-3p turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Further microRNAs which might own a link to the biology of the sulfur mustard patients are miR-365a-3p, miR-200a-3p, miR-663a. miR-148a-3p, which showed up only in a validation study, might be linked to the airway complications of the sulfur mustard patients. All the other candidate microRNAs do not directly link to COPD phenotype or lung complications. In summary the microRNA screening study characterizes several molecular differences in-between the clinical categories of the sulfur mustard exposure groups and established some useful microRNA biomarkers. qPCR raw data is available via the Gene Expression Omnibus https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110797.

The crucial choice of reference genes: identification of miR-191-5p for normalization of miRNAs expression in bone marrow mesenchymal stromal cell and HS27a/HS5 cell lines

“…In haematology, miR-191-5p is overexpressed in poor prognostic acute myeloid leukaemia 47 . miR-16 is the most frequently used as RG in several models and in circulating miRNA analysis [48][49][50][51][52][53][54][55] but always with another miR. miR-16 is the most frequently used as RG in several models and in circulating miRNA analyses, always combined with another miR.…”

MicroRNA‑150‑5p and SRC kinase signaling inhibitor 1 involvement in the pathological development of gastric cancer

“…Many studies have determined the role of miRNAs in the development of various diseases (7,(30)(31)(32) and further research has revealed that miRNAs are involved in the development of various types of cancer (33-36). Many studies have also identified the aberrant expression of certain miRNAs in tumor cells and thus are considered novel references for tumor diagnosis (37,38). miRNAs are novel therapeutic targets and may serve as prognostic indicators (34).…”

MicroRNA‐mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard

“…Sulfur mustard (SM; bis(2‐chloroethyl) sulfide), a potent vesicant 1 used against humans, continues to be recognized as a threat agent 2,3 . Stockpiles of SM and similar chemicals still exist, and the threat of intentional or accidental exposures is ever increasing 4,5 .…”

“…Growing evidence suggests that nucleic acids, including microRNAs (miRNAs), can influence the inflammation and coagulation pathways as well as other pathways involved in tissue injury and repair. Recent data have indicated the presence of altered expression of miRNAs in SM‐exposed individuals, 1 and a possible role of miRNAs in determining sensitivity to SM 17 . However, beyond preliminary reports on the differential expression of individual miRNAs in SM‐induced injury, not much is known.…”