Differential expression of cancer associated plasma miRNAs in the ordnance factory workers, exposed to 2,4,6-Trinitrotoluene.

OBJECTIVES

To determine differential expression of microRNAs (miRNAs) in plasma of 2, 4, 6-Trinitrotoluene (TNT) exposed ordnance factory workers.

METHODS

A case control study was conducted at the Department of Toxicology, Armed Forces Institute of Pathology, Rawalpindi from July to December 2020. A total 30 subjects were recruited from an ordnance factory that were directly exposed to TNT and 120 non-exposed individuals from non-factory healthy population. Plasma levels of five miRNAs including miRNA-let-7a-2, miRNA-34a-1, miRNA-21-2, miRNA-106b-1, miRNA-122a-1 were measured by quantitative real-time polymerase chain reaction (RT-PCR).

RESULTS

Micro RNAs showed a wide range of Ct (cycle threshold) values ranging from 23.48 to 41.94. Among the five miRNAs let-7a-2 and miRNA-122a-1 displayed relatively high expression with Ct values ranging from 26.58 ± 2.25 to 27.18 ± 0.80 respectively. Relative fold change expression for all five miRNAs of exposed individuals were found high ( <0.0001) vs non-exposed. Dividing fold change expression of exposed individuals into two groups as ≤ 10 and > 10, the individuals having ≤ 10-fold change expression were19 (63.3%) in miRNA-let-7a-2, 30 (100%) in miRNA-34a-1 and 23 (76.7%) in miRNA-122a-1 while in miRNA-21-2 and miR-106b-1, 23 (76.7%) and 18(60%) individuals had > 10-fold change expression respectively. Among the five miRNAs in exposed individuals, miRNA-let-7a-2, miR-21-2, miR-106b-1 and miR-122a-1 were found highly expressed with fold change expression > 10 ( <0.0001). No significant association was found between miRNAs expression levels with age and working duration.

CONCLUSION

The study shows upregulation of all five miRNAs in TNT exposed subjects with no significant association of expression levels with age and working duration