MicroRNA expression profiling in sulfur mustard exposed patients: biological significance and diagnostic utility.

Sulfur mustard (SM) is an active vesicating agent which was used against both military and civilian population of Iran during the Iran-Iraq war (1980-1988). Due to its unclear mechanism of action in pathogenesis of lung, clinical management strategies, especially diagnostic protocols and treatment are not well defined. microRNAs are promising biomarkers that could significantly discriminate different pathological and biological states among diseases and organs failure. MoreovermicroRNAs could be stably detected in bio-fluids like serum that grantee them as non-invasive biomarkers. We profiled739 microRNAs in serum samples of 43 SM exposed patients and 27 matched healthy volunteers. Expression patterns offive highly altered microRNAs including mir-663, miR-148a and miR-143-3p were further validated by real-time qPCR. microRNA profile analysis identified statistical unique microRNA panel, which could significantly distinguish patients with three pathological states: mild, moderate and severe. This panel was also applicable on SM exposed veterans who had no clinically recorded symptoms. Bioinformatic analysis along with functional investigations showed that altered microRNAs were related to cell cycle arrest and senescence pathways which are in concordance to pathological manifests of patients. Our presented microRNAs panel could be used diagnostically with high accuracy for classifying SM exposed patients and also for choosing treatments strategies based on molecular status of the disease