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Toxicol In Vitro. 2017 Jun;41:92-101. doi: 10.1016/j.tiv.2017.02.020. Epub 2017 Feb 27.

Comparative analysis of microRNA and mRNA expression profiles in cells and exosomes under toluene exposure.

Author information

1
Center for Environment, Health and Welfare Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Pharmacology and Toxicology, Human and Environmental Toxicology, Korea University of Science and Technology, Gajeong-Ro 217, Yuseong-gu, Daejeon 305-350, Republic of Korea.
2
National Center for Efficacy Evaluation for Respiratory Disease Product, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup, Jeollabuk-do 53212, Republic of Korea.
3
Center for Environment, Health and Welfare Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
4
Department of Pharmacology and Toxicology, Human and Environmental Toxicology, Korea University of Science and Technology, Gajeong-Ro 217, Yuseong-gu, Daejeon 305-350, Republic of Korea.
5
Center for Environment, Health and Welfare Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Biotechnology, Korea University, Seoul 02841,Republic of Korea. Electronic address: ryujc@kist.re.kr.

Abstract

Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells. Four out of the 54 miRNAs (hsa-miR-1290, hsa-miR-718, hsa-miR-3663-3p, and hsa-miR-320c) were subsequently validated by qRT-PCR. Integrated analysis of miRNA and mRNA expression profiles identified 8 miRNA-mRNA correlations. By performing Comparative Toxicogenomics Database analysis, we found that the eight putative target genes of the differentially expressed miRNAs under toluene exposure (EXOSC6, RHOH, GFER, HERC2, GOLGA4, SLC7A11, GCLM, and BACH1) are related to diverse disease categories such as nervous system disease, cancer, cardiovascular disease, and respiratory tract disease. In conclusion, our data demonstrated that miRNA-mRNA networks provide a better understanding of toxicological mechanism caused by environmental pollutants in vitro using HL-60 cells and exosomes.

KEYWORDS:

Exosome; HL-60; MicroRNA; Microarray; Target mRNA; Toluene

PMID:
28245982
DOI:
10.1016/j.tiv.2017.02.020
[Indexed for MEDLINE]

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