Identification of potential pathways and microRNA-mRNA networks associated with benzene metabolite hydroquinone-induced hematotoxicity in human leukemia K562 cells

Abstract

Background: Hydroquinone (HQ) is a phenolic metabolite of benzene with a potential risk for hematological disorders and hematotoxicity in humans. In the present study, an integrative analysis of microRNA (miRNA) and mRNA expressions was performed to identify potential pathways and miRNA-mRNA network associated with benzene metabolite hydroquinone-induced hematotoxicity. Methods: K562 cells were treated with 40 μM HQ for 72 h, mRNA and miRNA expression changes were examined using transcriptomic profiles and miRNA microarray, and then bioinformatics analysis was performed. Results: Out of all the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) induced by HQ, 1482 DEGs and 10 DEMs were up-regulated, and 1594 DEGs and 42 DEMs were down-regulated. HQ-induced DEGs were involved in oxidative stress, apoptosis, DNA methylation, histone acetylation and cellular response to leukemia inhibitory factor GO terms, as well as metabolic, Wnt/β-catenin, NF-κB, and leukemia-related pathways. The regulatory network of mRNAs and miRNAs includes 23 miRNAs, 1108 target genes, and 2304 potential miRNAs-mRNAs pairs. MiR-1246 and miR-224 had the potential to be major regulators in HQ-exposed K562 cells based on the miRNAs-mRNAs network. Conclusions: This study reinforces the use of in vitro model of HQ exposure and bioinformatic approaches to advance our knowledge on molecular mechanisms of benzene hematotoxicity at the RNA level.