Benzene-Induced Aberrant miRNA Expression Profile in Hematopoietic Progenitor Cells in C57BL/6 Mice

Abstract

Benzene is a common environmental pollutant that causes hematological alterations. MicroRNAs (miRNAs) may play a role in benzene-induced hematotoxicity. In this study, C57BL/6 mice showed significant hematotoxicity after exposure to 150 mg/kg benzene for 4 weeks. Benzene exposure decreased not only the number of cells in peripheral blood but also hematopoietic progenitor cells in the bone marrow. Meanwhile, RNA from Lin− cells sorted from the bone marrow was applied to aberrant miRNA expression profile using Illumina sequencing. We found that 5 miRNAs were overexpressed and 45 miRNAs were downregulated in the benzene exposure group. Sequencing results were confirmed through qRT-PCR. Furthermore, we also identified five miRNAs which significantly altered in Lin−c-Kit+ cells obtained from benzene-exposed mice, including mmu-miR-34a-5p; mmu-miR-342-3p; mmu-miR-100-5p; mmu-miR-181a-5p; and mmu-miR-196b-5p. In summary, we successfully established a classical animal model to induce significant hematotoxicity by benzene injection. Benzene exposure may cause severe hematotoxicity not only to blood cells in peripheral circulation but also to hematopoietic cells in bone marrow. Benzene exposure also alters miRNA expression in hematopoietic progenitor cells. This study suggests that benzene induces alteration in hematopoiesis and hematopoiesis-associated miRNAs.

Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis

“…hsa‐miR‐196b‐5p, hsa‐miR‐301a‐3p, and hsa‐miR‐532‐5p have already been reported to be associated with immune cell function and to be related to inflammatory conditions. miR‐196b has been frequently found in various hematopoietic cell populations, both normal and neoplasmatic . miR‐301a presence has been related to various immune and autoaggressive conditions, including MS .…”

“…miR-196b has been frequently found in various hematopoietic cell populations, both normal and neoplasmatic. [30][31][32] miR-301a presence has been related to various immune and autoaggressive conditions, including MS. 7,[33][34][35][36][37] In this regard, we have previously reported on the critical role of miR-301a as an endogenous regulator of Th17 development in an animal model of MS. 7 miR-532 has also been reported to be expressed by PBMCs and to be linked to gender differences in rheumatoid arthritis susceptibility. 38 miR-532-5p expression in MS PBMCs has been found to be downregulated during interferon-b treatment.…”

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

“…An association between benzene and aberrant miRNA expression was also reported in a non-occupational setting: miR-223 expression in pregnant women and indoor dwelling concentrations of benzene and toluene (smoking-related volatile organic compounds) were positively associated and appeared to decrease the number of regulatory T-cells in maternal and cord blood [125]. Mice that were injected with benzene for 4 weeks showed significant hematotoxicity, as well as changes in expression of several miRNAs in the bone marrow cells of exposed mice: 5 miRNAs were over-expressed and 45 miRNAs were downregulated [126]. The over-expressed miRNAs were miR-34a-5p, miR-129b-5p, miR-451a, miR-144-5p and miR-129b-3p, and the most highly down-regulated miRNAs were miR-33-5p, miR-128-1-5p, miR-188-5p, miR-211-5p, miR-224-5p, miR-504-5p, miR-5107-3p, miR-5120, and let-7i-3p.…”

Exosomal miR‐221 derived from hydroquinone‐transformed malignant human bronchial epithelial cells is involved in cell viability of recipient cells

“…Although the International Agency for Research on Cancer (IARC) classifies benzene as a Group 1 human carcinogen (IARC, 2019), the mechanism of its carcinogenesis through which it exerts its carcinogenic potential remains largely unclear. Accumulating evidence indicates that miRNAs play important roles in the toxic effects of benzene (Fenga, Gangemi, & Costa, 2016;Luo et al, 2018;Rommer et al, 2013;Wei et al, 2015). Our study revealed that normal cells (16HBE) can be transformed into malignant ones by HQ (an active metabolite of benzene), and that miR-221 has an elevated expression level in HQ-transformed malignant cells.…”