Integrative analyses of circulating microRNA expression profile in hexavalent chromium exposed workers - A cross-sectional study within the SafeChrom project

Abstract

Background: Exposure to hexavalent chromium (Cr(VI)) can occur during occupational activities and leading lung cancer. MicroRNA (miRNA) plays an important part in carcinogenesis. Whether Cr(VI) exposure causes cancer-related miRNA changes is yet uncharacterized.

Methods: This study included 89 Cr(VI) exposed workers and 47 controls. MiRNAs were extracted from plasma followed by library preparations, miRNA sequencing, and differentially expressed miRNAs (DEMs) analysis. To understand the underlying biological functions, we used bioinformatics approaches, and qPCR was performed to validate the expression of potential target genes.

Results: A total of 2100 miRNAs were detected. In the exposed workers, 59 DEMs were identified: 21 up-regulated and 38 down-regulated. Target genes for both up- and down-regulated DEMs were significantly enriched in: miRNAs in cancer, small cell lung cancer and non-small cell lung cancer. Protein-protein interactions showed a high number of interactions, in which CCNE2, CDK4 and E2F1 were predicted as hub genes, and the messenger RNA expression of those genes was significantly higher in the exposed workers compared with controls.

Conclusions: Our study suggests that low-to-moderate Cr(VI) exposure results in differential expression of lung-cancer-related miRNAs and associated target genes. Further studies are needed to validate our findings and clarify whether these changes predict cancer risk.

Keywords: Bioinformatics; Expression profiles; Hexavalent chromium; MicroRNA; Sequencing.