Skip to main content

Expression of exosomal and cellular microRNAs: as biomarkers for toluene, ethylbenzene, xylene (TEX) exposure

Molecular & Cellular Toxicology volume 12, pages 359–369 (2016)Cite this article

Abstract

Exosomes, small vesicles released by many cells, are associated with various biological processes and they can potentially be used for prognosis and therapy and as biomarkers of health. Thus, they are gaining attention in toxicological and pathological research. miRNA is also considered as a useful tool to predict health risk caused by environmental toxicants. Volatile organic compounds (VOCs), including toluene (T), xylene (X), and ethylbenzene (E), have been reported to be harmful. Although VOCs are prevalent in the environment, the mechanisms underlying their toxicity are not understood. In this study, a microarray analysis identified 50 miRNAs that were differentially expressed in exosomes and cytosols of HL-60 cell line exposed to three VOCs (TEX). A total of 3,355 putative target genes were classified according to the miRWalk 2.0 database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the putative target genes showed a correlation with biological processes involved in the regulation of myeloid leukocyte differentiation, MAPK signaling pathway, and pathways in cancer. In conclusion, this study describes alterations in miRNA expression profiles in response to exposure to VOCs and related toxicity affected by significantly expressed target genes. Moreover, it illustrates the value of exosomes as diagnostic biomarkers of toxicity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

39,95 €

Price includes VAT (Finland)

References

  1. Kharaziha, P., Ceder, S., Li, Q. & Panaretakis, T. Tumor cell-derived exosomes: a message in a bottle. BBAREV CANCER 1826:103–111 (2012).

    CAS  Google Scholar 

  2. Feng, D. Q. et al. Selective miRNA expression profile in chronic myeloid leukemia K562 cell-derived exosomes. APJCP 14:7501–7508 (2013).

    PubMed  Google Scholar 

  3. O’Brien, K. et al. Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. Eur J Cancer 49:1845–1859 (2013).

    Article  PubMed  Google Scholar 

  4. Lobb, R. J. et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. JEV 4:27031 (2015).

    PubMed  Google Scholar 

  5. Taylor, D. D. & Gercel-Taylor, C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Song, M. K. & Ryu, J. C. Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC). Int J Hyg Environ Health 218:590–602 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Guo, H., Murray, F. & Wilkinson, S. Evaluation of total volatile organic compound emissions from adhesives based on chamber tests. J Air Waste Manage Assoc 50: 199–206 (2000).

    Article  CAS  Google Scholar 

  8. Ten Brinke, J. et al. Development of new volatile organic compound (VOC) exposure metrics and their relationship to “sick building syndrome” symptoms. Indoor Air 8:140–152 (1998).

    Article  CAS  Google Scholar 

  9. Yu, C. & Crump, D. A review of the emission of VOCs from polymeric materials used in buildings. Build Environ 33:357–374 (1998).

    Article  Google Scholar 

  10. Benignus, V. A. Health effects of toluene: a review. Neurotoxicology 2:567–588 (1981).

    CAS  PubMed  Google Scholar 

  11. Cho, Y., Lim, J. H., Jeong, S. C., Song, M. K. & Ryu, J. C. Hexanal-induced changes in miRNA-mRNA interactions in A549 human alveolar epithelial cells. J Toxicol Environ Health Sci 7:143–159 (2015).

    Article  Google Scholar 

  12. Ahn, J. I. et al. Changes of miRNA and mRNA expression in HepG2 cells treated by epigallocatechin gallate. Mol Cell Toxicol 6:169–177 (2010).

    Article  CAS  Google Scholar 

  13. Lu, J. et al. MicroRNA expression profiles classify human cancers. Nature 435:834–838 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Cha, H. J. et al. MicroRNA expression profiling of pphenylenediamine treatment in human keratinocyte cell line. Mol Cell Toxicol 11:19–28 (2015).

    Article  CAS  Google Scholar 

  15. Saikumar, J. et al. Expression, Circulation, and Excretion Profile of MicroRNA-21, -155, and -18a Following Acute Kidney Injury. Toxicol Sci 129:256–267 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Michael, A. et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 16:34–38 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Gallagher, R. et al. Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood 54:713–733 (1979).

    CAS  PubMed  Google Scholar 

  18. Kondoh, M. et al. Cadmium induces apoptosis partly via caspase-9 activation in HL-60 cells. Toxicology 170: 111–117 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Ruiz-Ramos, R., Cebrian, M. E. & Garrido, E. Benzoquinone activates the ERK/MAPK signaling pathway via ROS production in HL-60 cells. Toxicology 209: 279–287 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Salomon, C. et al. in The role of placental exosomes in gestational diabetes mellitus (IN TECH Open Access Publisher, 2013).

    Book  Google Scholar 

  21. Farh, K. K. et al. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310:1817–1821 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Song, M. K. et al. Analysis of microRNA and mRNA expression profiles highlights alterations in modulation of the MAPK pathway under octanal exposure. Environ Toxicol Phar 37:84–94 (2014).

    Article  CAS  Google Scholar 

  23. Huang, X. et al. Exosomal miR-1290 and miR-375 as prognostic markers in metastatic castrate resistant prostate cancer. EUR UROL 74:574–574 (2014).

    Google Scholar 

  24. Leng, R., Zha, L. & Tang, L. MiR-718 represses VEGF and inhibits ovarian cancer cell progression. FEBS Lett 588:2078–2086 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Soon, P. S. H. et al. miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer. Clin Cancer Res 15:7684–7692 (2009).

    Article  CAS  PubMed  Google Scholar 

  26. Chabre, O. et al. Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients. Endocr-Relat Cancer 20:579–594 (2013).

    CAS  PubMed  Google Scholar 

  27. Fagliano, J., Berry, M., Bove, F. & Burke, T. Drinking water contamination and the incidence of leukemia: an ecologic study. Am J Public Health 80:1209–1212 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cazzalini, O., Scovassi, A. I., Savio, M., Stivala, L. A. & Prosperi, E. Multiple roles of the cell cycle inhibitor p21 (CDKN1A) in the DNA damage response. Mutat Res 704:12–20 (2010).

    Article  CAS  PubMed  Google Scholar 

  29. Warren, D. T. et al. Novel nuclear nesprin-2 variants tether active extracellular signal-regulated MAPK1 and MAPK2 at promyelocytic leukemia protein nuclear bodies and act to regulate smooth muscle cell proliferation. J Biol Chem 285:1311–1320 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Caron de Fromentel, C. & Soussi, T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer 4:1–15 (1992).

  31. Lema, C. & Cunningham, M. J. MicroRNAs and their implications in toxicological research. Toxicol Lett 198: 100–105 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63 (1983).

    Article  CAS  PubMed  Google Scholar 

  33. Dweep, H. & Gretz, N. miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods 12: 697 (2015).

    Article  CAS  PubMed  Google Scholar 

  34. Benjamini, Y. & Hochberg, Y. Controlling the False Discovery Rate -a Practical and Powerful Approach to Multiple Testing. J Roy Stat Soc B Met 57:289–300 (1995).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Environment, Health and Welfare Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea

    Jung-hee Lim, Yoon Cho, Woong Kim & Jae-Chun Ryu

  2. Department of Pharmacology and Toxicology, Human and Environmental Toxicology, Korea University of Science and Technology, Gajeong-Ro 217, Yuseong-gu, Daejeon, 34113, Republic of Korea

    Jae-Chun Ryu

  3. Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea

    Jung-hee Lim & Sung Ok Han

  4. 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

    Mi-Kyung Song

Authors
  1. Jung-hee Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mi-Kyung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoon Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Woong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung Ok Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jae-Chun Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae-Chun Ryu.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lim, Jh., Song, MK., Cho, Y. et al. Expression of exosomal and cellular microRNAs: as biomarkers for toluene, ethylbenzene, xylene (TEX) exposure. Mol. Cell. Toxicol. 12, 359–369 (2016). https://doi.org/10.1007/s13273-016-0040-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-016-0040-z

Keywords

  • Exosome
  • miRNA
  • VOCs
  • Microarray
  • HL-60
  • Biomarker