BioChip Journal

, Volume 9, Issue 3, pp 239–246 | Cite as

Integrative analysis of miRNA and mRNA profiles in response to myricetin in human endothelial cells

  • Seung Eun Lee
  • Gun Woo Son
  • Hye Rim Park
  • Young-Ho Jin
  • Cheung-Seog Park
  • Yong Seek Park
Original Article


MicroRNAs (miRNAs) are associated with a diverse range of biological processes, human diseases, and metabolic disorders. Myricetin, which is the most abundant polyphenol class in the human diet, has antioxidative, antiapoptotic, and anti-inflammatory properties. The present study aimed to evaluate whether myricetin modulates miRNA expression. Using microarray analysis, we investigated miRNA expression in human endothelial cells treated with 25 µM and 100 µM of myricetin for 24 hours, and found that 101 and 191 miRNAs, respectively, were differential expressed by at least 1.5-fold. Based on several bioinformatic systems, we also identified signatures of the potential biological processes and signaling pathways that are influenced by dysregulated miRNAs. Therefore, integrating specific patterns of miRNA and mRNA levels may suggest a new mechanism of action of myricetin.


Endothelial cells Myricetin Polyphenol miRNA Vascular diseases 


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  1. 1.
    Gutierrez, E. et al. Endothelial dysfunction over the course of coronary artery disease. Eur. Heart J. 34, 3175–3181 (2013).CrossRefGoogle Scholar
  2. 2.
    Sumpio, B.E., Riley, J.T. & Dardik, A. Cells in focus: endothelial cell. Int. J. Biochem. Cell Biol. 34, 1508–1512 (2002).CrossRefGoogle Scholar
  3. 3.
    Lee, S.E. & Park, Y.S. The role of antioxidant enzymes in adaptive responses to environmental toxicants in vascular disease. Mol. Cell. Toxicol. 9, 95–101 (2013).CrossRefGoogle Scholar
  4. 4.
    Lee, S.E. & Park, Y.S. Role of lipid peroxidation-derived alpha, beta-unsaturated aldehydes in vascular dysfunction. Oxid. Med. Cell Longev. 2013, 629028 (2013).Google Scholar
  5. 5.
    Dauchet, L. et al. Frequency of fruit and vegetable consumption and coronary heart disease in France and Northern Ireland: the PRIME study. Br. J. Nutr. 92, 963–972 (2004).CrossRefGoogle Scholar
  6. 6.
    Chanet, A. et al. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J. Nutr. Biochem. 23, 469–477 (2012).CrossRefGoogle Scholar
  7. 7.
    Zelus, C. et al. Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity. Open Biochem. J. 6, 66–70 (2012).CrossRefGoogle Scholar
  8. 8.
    Borde, P., Mohan, M. & Kasture, S. Effect of myricetin on deoxycorticosterone acetate (DOCA)-salt-hypertensive rats. Nat. Prod. Res. 25, 1549–1559 (2011).CrossRefGoogle Scholar
  9. 9.
    Lee, Y.S. & Choi, E.M. Myricetin inhibits IL-1beta-induced inflammatory mediators in SW982 human synovial sarcoma cells. Int. Immunopharmacol. 10, 812–814 (2010).CrossRefGoogle Scholar
  10. 10.
    Wang, S.J. et al. Anti-inflammatory Activity of Myricetin Isolated from Myrica rubra Sieb. et Zucc. Leaves. Planta Med. 76, 1492–1496 (2010).CrossRefGoogle Scholar
  11. 11.
    Yi, L. et al. Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction. Int. J. Mol. Sci. 12, 5471–5489 (2011).CrossRefGoogle Scholar
  12. 12.
    Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116, 281–297 (2004).CrossRefGoogle Scholar
  13. 13.
    Zeng, Y. Principles of micro-RNA production and maturation. Oncogene. 25, 6156–6162 (2006).CrossRefGoogle Scholar
  14. 14.
    Hayashita, Y. et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65, 9628–9632 (2005).CrossRefGoogle Scholar
  15. 15.
    Jovanovic, M. & Hengartner, M.O. miRNAs and apoptosis: RNAs to die for. Oncogene. 25, 6176–6187 (2006).CrossRefGoogle Scholar
  16. 16.
    Schickel, R., Boyerinas, B., Park, S.M. & Peter, M.E. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogen. 27, 5959–5974 (2008).CrossRefGoogle Scholar
  17. 17.
    Joshi, S.R., McLendon, J.M., Comer, B.S. & Gerthoffer, W.T. MicroRNAs-control of essential genes: Implications for pulmonary vascular disease. Pulm Circ. 1, 357–364 (2011).CrossRefGoogle Scholar
  18. 18.
    Sayed, A.S., Xia, K., Salma, U., Yang, T. & Peng, J. Diagnosis, prognosis and therapeutic role of circulating miRNAs in cardiovascular diseases. Heart, lung & circulatio. 23, 503–510 (2014).CrossRefGoogle Scholar
  19. 19.
    Lee, S.E. et al. MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect. J. Pineal Res. 51, 345–352 (2011).CrossRefGoogle Scholar
  20. 20.
    Zhang, Y.Q. et al. Expression profiling and pathway analysis of microRNA expression in the lungs of mice exposed to long-term, low-dose benzo(a)pyrene. Mol. Cell. Toxicol. 10, 67–74 (2014).CrossRefGoogle Scholar
  21. 21.
    Yang, H. et al. An integrated analysis of microRNA and mRNA expression in salvianolic acid B-treated human umbilical vein endothelial cells. Mol. Cell. Toxicol. 9, 1–7 (2013).CrossRefGoogle Scholar
  22. 22.
    Katoh, M. Therapeutics targeting angiogenesis: genetics and epigenetics, extracellular miRNAs and signaling networks (Review). Int. J. Mol. Med. 32, 763–767 (2013).Google Scholar
  23. 23.
    An, Y.R. & Hwang, S.Y. Toxicology study with microRNA. Mol. Cell. Toxicol. 10, 127–134 (2014).CrossRefGoogle Scholar
  24. 24.
    An, Y.R. et al. Functional analysis of endocrine disruptor pesticides affected transcriptome and microRNA regulation in human hepatoma cell line. Mol. Cell. Toxicol. 10, 393–400 (2014).CrossRefGoogle Scholar
  25. 25.
    Yang, H. et al. Integrated analysis of miRNA and mRNA reveals that acrolein modulates GPI anchor biosynthesis in human primary endothelial cells. Biochip J. 7, 11–16 (2013).CrossRefGoogle Scholar
  26. 26.
    Dennis, G. ffixJr. et al. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4, P3 (2003).CrossRefGoogle Scholar
  27. 27.
    Hirose, E. et al. Involvement of Heme Oxygenase-1 in Kaempferol-Induced Anti-Allergic Actions in RBL-2H3 Cells. Inflammation. 32, 99–108 (2009).CrossRefGoogle Scholar
  28. 28.
    Lin, H.Y., Juan, S.H., Shen, S.C., Hsu, F.L. & Chen, Y.C. Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. Biochem. Pharmacol. 66, 1821–1832 (2003).CrossRefGoogle Scholar
  29. 29.
    Ozcan, F., Ozmen, A., Akkaya, B., Aliciguzel, Y. & Aslan, M. Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. Clin. Exp. Med. 12, 265–272 (2012).CrossRefGoogle Scholar
  30. 30.
    Choi, H.S., Song, M.K. & Ryu, J.C. Integrated analysis of microRNA and mRNA expression profiles highlights alterations in modulation of the apoptosis-related pathway under nonanal exposure. Mol. Cell Toxicol. 9, 351–364 (2013).CrossRefGoogle Scholar
  31. 31.
    Saunders, M.A. & Lim, L.P. (micro)genomic medicine microRNAs as therapeutics and biomarkers. RNA Biol. 6, 324–328 (2009).CrossRefGoogle Scholar
  32. 32.
    Choi, B.J. et al. GKN1 and miR-185 are associated with CpG island methylator phenotype in gastric cancers. Mol. Cell. Toxicol. 9, 227–233 (2013).CrossRefGoogle Scholar
  33. 33.
    Boren, T. et al. MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis. Gynecol. Oncol. 110, 206–215 (2008).CrossRefGoogle Scholar
  34. 34.
    Blower, P.E. et al. MicroRNA expression profiles for the NCI-60 cancer cell panel. Mol. Cancer Ther. 6, 1483–1491 (2007).CrossRefGoogle Scholar
  35. 35.
    Jeong, S.C., Shin, C.Y., Song, M.K., Cho, Y. & Ryu, J.C. Gene expression profiling of human alveolar epithelial cells (A549 cells) exposed to atmospheric particulate matter 2.5 (PM2.5) collected from Seoul, Korea. Mol. Cell. Toxicol. 10, 361–368 (2014).CrossRefGoogle Scholar

Copyright information

© The Korean BioChip Society and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Seung Eun Lee
    • 1
  • Gun Woo Son
    • 1
  • Hye Rim Park
    • 1
  • Young-Ho Jin
    • 2
  • Cheung-Seog Park
    • 1
  • Yong Seek Park
    • 1
  1. 1.Department of Microbiology, School of MedicineKyung Hee UniversitySeoulKorea
  2. 2.Department of Physiology, School of MedicineKyung Hee UniversitySeoulKorea

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