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Changes of miRNA and mRNA expression in HepG2 cells treated by epigallocatechin gallate

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Abstract

Epigallocatechin gallate (EGCG), a major type of green tea polyphenol, has been reported to cause hepatotoxicity when used in excess. Micro-RNAs (miRNAs) are small non-coding RNA molecules that functions as negative regulators of gene expression. They play an important role in the regulation of genes involved in the cellular and molecular responses to toxicants. To examine miRNA regulatory effect on global gene expression in EGCG-treated HepG2 cells, we performed pair-wise correlation coefficient analysis on expression levels of 22 miRNA and 27,419 mRNA, and observed negative correlations (r< −0.7) between miRNA and mRNA. We identified a total of 234 negative correlated miRNA-mRNA pairs. Gene Ontology analysis on the miRNA-correlated genes revealed significant enrichment in the several biological processes related to organic acid metabolic process, carboxylic acid metabolic process and cellular protein catabolic process. Connectivity map analysis also revealed that the expression signatures of EGCG were very similar to those of polyphenol gossypol which is hepatotoxic to animal and human.

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References

  1. Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Wu, L. & Belasco, J. G. Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell 29:1–7 (2008).

    Article  PubMed  Google Scholar 

  3. Griffiths-Jones, S., Saini, H. K., van Dongen, S. & Enright, A. J. miRBase: tools for microRNA genomics. Nucleic Acids Res 36(Database issue):D154–158. Epub (2007).

    Article  PubMed  Google Scholar 

  4. Miska, E. A. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 15: 563–568 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Ørom, U. A., Nielsen, F. C. & Lund, A. H. Micro-RNA-10a binds the 5’UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460–471 (2008).

    Article  PubMed  Google Scholar 

  6. Isbrucker, R. A. et al. Safety studies on epigallocatechin gallate (EGCG) preparation. Part3: teratogenecity and reproductive toxicity studies in rats. Food Chem Toxicol 44:651–661 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Galati, G., Lin, A., Sultan, A. M. & O’Brien, P. J. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med 40:570–580 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Pennie, W. D., Woodyatt, N. J., Aldridge, T. C. & Orphanides, G. Application of genomics to the definition of the molecular basis for toxicity. Toxicol Lett 120:353–358 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Hudder. A. & Novak, R. F. miRNAs: effectors of environmental influences on gene expression and disease. Toxicol Sci 103:228–240 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. Wang, L. et al. Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines. PLoS One 4:e5878 (2009).

    Article  PubMed  Google Scholar 

  11. Liu, T. et al. Detection of a microRNA signal in an in vivo expression set of mRNAs. PLoS One 2:e804 (2007).

    Article  PubMed  Google Scholar 

  12. Gammell, P. MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells: Identification of miRNAs regulating growth and survival. Cytotechnology 53:55–63 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Diodovich, C. et al. Modulation of different stress pathways after styrene and styrene-7, 8-oxide exposure in HepG2 cell line and normal human hepatocytes. J Appl Toxicol 26:317–325 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Hwang, H. W. & Mendell, J. T. MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer 94:776–780 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Elliott, M. J., Dong, Y. B., Yang, H. & McMasters, K. M. E2F-1 up-regulates c-Myc and p14 (ARF) and induces apoptosis in colon cancer cells. Clin Cancer Res 7:3590–3597 (2001).

    CAS  PubMed  Google Scholar 

  16. Janumyan, Y. M. et al. Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry. EMBO J 22:5459–5470 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Ahn, J. I. et al. High-concentration epigallocatechin gallate treatment causes endoplasmic reticulum stressmediated cell death in HepG2 cells. Genomics & Informatics 7:97–106 (2009).

    Google Scholar 

  18. Lynn, F. C. Meta-regulation: microRNA regulation of glucose and lipid metabolism. Trends Endocrinol Metab 20:452–459 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Nichols, K. D. & Kirby, G. M. Microarray analysis of hepatic gene expression in pyrazole-mediated hepatotoxicity: identification of potential stimuli of Cyp2a5 induction. Biochem Pharmacol 75:538–551 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Gilmore, W. J. & Kirby, G. M. Endoplasmic reticulum stress due to altered cellular redox status positively regulates murine hepatic CYP2A5 expression. J Pharmacol Exp Ther 308:600–608 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Cheng, J. S. et al. Effect of gossypol on intracellular Ca2+ regulation in human hepatoma cells. Chin J Physiol 46:117–122 (2003).

    CAS  PubMed  Google Scholar 

  22. Lei, X. et al. Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2. FASEB J 20:2147–2149 (2006).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Ho-Sang Jeong.

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Ahn, JI., Jeong, K.J., Ko, MJ. et al. Changes of miRNA and mRNA expression in HepG2 cells treated by epigallocatechin gallate. Mol. Cell. Toxicol. 6, 169–177 (2010). https://doi.org/10.1007/s13273-010-0024-3

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  • DOI: https://doi.org/10.1007/s13273-010-0024-3

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