Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning.

BACKGROUND

Circulating microRNA (miRNA) has attractive interests as a non-invasive biomarker of physiological and pathological conditions. Our study aimed to investigate the potential effects of chronic benzene poisoning (CBP) and benzene exposure on miRNA expression, and identify CBP-related miRNAs.

METHODS

In the discovery stage, we used a microarray assay to detect the miRNA expression profiles among pooled plasma samples from ten CBP patients, ten healthy benzene-exposed individuals and ten non-benzene exposed individuals. Subsequently, we conducted an expanded validation of six candidate miRNAs in 27 CBP patients- low blood counts, 54 healthy benzene-exposed individuals and 54 non-exposed individuals. Moreover, we predicted the biological functions of putative target genes using a Gene Ontology (GO) function enrichment analysis and KEGG pathway analysis.

RESULTS

In the discovery stage, compared with non-exposures, 36 and 12 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients and the benzene exposures, respectively. And compared with benzene exposures, 58 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients. In the expanded validation stage, compared with non-exposures as well as exposures, miR-24-3p and miR-221-3p were significantly up-regulated (1.99- and 2.06-fold for miR-24-3p, 2.19- and 3.93-fold for miR-221-3p, P<0.01) while miR-122-5p and miR-638 were significantly down-regulated (-3.45- and -2.60-fold for miR-122-5p, -1.82- and -3.20-fold for miR-638, P<0.001) in the CBP patients; compared with non-exposures, the plasma level of miR-638 was significantly up-regulated (1.38-fold, P<0.01) while the plasma levels miR-122-5p and miR-221-3p were significantly down-regulated (-0.85- and -1.74-fold, P<0.01) in the exposures, which were consistent with the results of microarray analysis.

CONCLUSIONS

The four indicated plasma miRNAs may be biomarkers of indicating responses to benzene exposure. Further studies are warranted to verify our findings with a large sample and to confirm the underlying mechanisms.