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Analysis of miRNA expression profiling in melatonin-exposured endothelial cells

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Abstract

Melatonin is produced from tryptophan and is secreted by the pineal gland in periods of darkness; it has cytoprotective effects in endothelial cells. It has been reported that melatonin mediates the regulation of gene expression at the post-transcriptional level through its effect on miRNA expression. miRNAs are small non-coding RNAs that silence gene expression, regulate most cellular processes involved in development, and maintain cell functions. In this study, we confirmed the expression of 136 and 154 miRNAs when endothelial cells were treated with melatonin concentrations of 100 μM and 1 mM, respectively. We investigated anti-correlations in miRNA-target-mRNA pairs, and we identified a total of 13 and 44 mRNAs showing an expression difference of >1.5 fold, following exposure to melatonin concentrations of 100 μM and 1 mM, respectively. These profiling data revealed a variety of biological effects, including cell death, apoptosis and proliferation, via a Gene Ontology analysis of biological processes. The results of this study suggest that melatonin may regulate miRNA and gene expression and may have a cytoprotective effect on endothelial cells.

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References

  1. Tocharus, C. et al. Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor. Neuroscience 275C:314–321 (2014).

    Article  Google Scholar 

  2. Reiter, R. J., Tamura, H., Tan, D. X. & Xu, X. Y. Melatonin and the circadian system: contributions to successful female reproduction. Fertil Steril 102:321–328 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Trivedi, A. K. & Kumar, V. Melatonin: an internal signal for daily and seasonal timing. Indian J Exp Biol 52:425–437 (2014).

    CAS  PubMed  Google Scholar 

  4. Dubocovich, M. L., Rivera-Bermudez, M. A., Gerdin, M. J. & Masana, M. I. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci 8:d1093–1108 (2003).

    Article  Google Scholar 

  5. Audinot, V. et al. New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol 367:553–561 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Cajochen, C., Krauchi, K. & Wirz-Justice, A. Role of melatonin in the regulation of human circadian rhythms and sleep. J Neuroendocrinol 15:432–437 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Aygun, D., Kaplan, S., Odaci, E., Onger, M. E. & Altunkaynak, M. E. Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and diclofenac sodium association. Histol Histopathol 27:417–436 (2012).

    CAS  PubMed  Google Scholar 

  8. Vishwas, D. K., Mukherjee, A., Haldar, C., Dash, D. & Nayak, M. K. Improvement of oxidative stress and immunity by melatonin: an age dependent study in golden hamster. Exp Gerontol 48:168–182 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Goswami, S., Sharma, S. & Haldar, C. The oxidative damages caused by ultraviolet radiation type C (UVC) to a tropical roden Funambulus pennanti: role of melatonin. J Photochem Photobiol B 125:19–25 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Bai, J. et al. The role of melatonin as an antioxidant in human lens epithelial cells. Free Radical Research 47: 635–642 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Song, J. et al. Th Beneficial Effect of Melatonin in Brain Endothelial Cells against Oxygen-Glucose Deprivation Followed by Reperfusion-Induced Injury. Oxid Med Cell Longev 2014:639531 (2014).

    PubMed  PubMed Central  Google Scholar 

  12. Hu, Z. P. et al. Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF-kappaB system in highfat-fed rabbits. J Pineal Res 55:388–398 (2013).

    CAS  PubMed  Google Scholar 

  13. Alvarez-Garcia, V., Gonzalez, A., Alonso-Gonzalez, C., Martinez-Campa, C. & Cos, S. Antiangiogenic effects of melatonin in endothelial cell cultures. Microvasc Res 87:25–33 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Yang, L. et al. Melatoni Suppresses Hypoxia-Induced Migration of HUVECs via Inhibition of ERK/Rac1 Activation. Int J Mol Sci 15:14102–14121 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rodella, L. F. et al. Vascular endothelial cells and dysfunctions: role of melatonin. Front Biosci (Elite Ed) 5: 119–129 (2013).

    Google Scholar 

  16. Ingram, D. A. et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood 105:2783–2786 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Sumpio, B. E., Riley, J. T. & Dardik, A. Cells in focus: endothelial cell. Int J Biochem Cell Biol 34:1508–1512 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Kobayashi, H. et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circulation Research 94:E27–E31 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kuehbacher, A., Urbich, C., Zeiher, A. M. & Dimmeler, S. Role o Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 101:59–68 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Jeong, S. I. et al. MicroRNA microarray analysis of human umbilical vein endothelial cells exposed to benzo (a)pyrene. Biochip J 6:191–196 (2012).

    Article  CAS  Google Scholar 

  21. Fasanaro, P. et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283: 15878–15883 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhao, Y. et al. MicroRNA regulation of messenger-like noncoding RNA s: a network of mutual microRNA control. Trends Genet 24:323–327 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Baier, S. R., Nguyen, C., Xie, F., Wood, J. R. & Zempleni, J. MicroRNA Are Absorbed in Biologically Meaningful Amounts from Nutritionally Relevant Doses of Cow Milk and Affect Gene Expression in Peripheral Blood Mononuclear Cells, HEK-293 Kidney Cell Cultures, and Mouse Livers. J Nutr 144:1495–1500 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nadeem, U., Ye, G., Salem, M. & Peng, C. MicroRNA-378a-5 Targets Cyclin G2 to Inhibit Fusion and Differentiation in BeWo Cells. Biol Reprod 91:76 (2014).

    Article  PubMed  Google Scholar 

  25. Bjorner, S. et al. Epithelial an Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation. PLoS One 9:e105099 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Zhu, X. et al. MicroRNA-30e Suppresses Dengue Virus Replication by Promoting NF-kappaB-Dependent IFN Production. PLoS Negl Trop Dis 8:e3088 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kim, J. Y. et al. Genome-wide profiling of the micro RNA-mRNA regulatory network in skeletal muscle with aging. Aging (Albany NY) 6:524–544 (2014).

    Article  CAS  PubMed Central  Google Scholar 

  28. Doebele, C. et al. Members of the microRNA-17–92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood 115:4944–4950 (2010).

    Article  CAS  PubMed  Google Scholar 

  29. Hergenreider, E. et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNA s. Nature Cell Biology 14:249–256 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Wang, S. et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ramraj, S. K. et al. Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease. Oncotarget 7615 (2016).

    Google Scholar 

  32. Lee, S. E. et al. Genome-wide profiling in melatoninexposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin. J Pineal Res 54:80–88 (2013).

    CAS  PubMed  Google Scholar 

  33. 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).

    Article  CAS  PubMed  Google Scholar 

  34. Rodriguez, C. et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Shaikh, A. Y., Xu, J., Wu, Y., He, L. & Hsu, C. Y. Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA damage and death. Neurosci Lett 229:193–197 (1997).

    Article  CAS  PubMed  Google Scholar 

  36. Ahsen, A. et al. Protective effect of melatonin on infrarenal aortic occlusion: this effect is related to anti-inflammatory effect and antioxidant effect. Inflammation 37:1111–1119 (2014).

    Article  PubMed  Google Scholar 

  37. Bonnefont-Rousselot, D. Obesity an Oxidative Stress: Potential Roles of Melatonin as Antioxidant and Metabolic Regulator. Endocr Metab Immune Disord Drug Targets 14:159–168 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. Mauriz, J. L., Collado, P. S., Veneroso, C., Reiter, R. J. & Gonzalez-Gallego, J. A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J Pineal Res 54:1–14 (2013).

    CAS  PubMed  Google Scholar 

  39. Park, H. J. et al. Melatonin inhibits lipopolysaccharideinduced CC chemokine subfamily gene expression in human peripheral blood mononuclear cells in a microarray analysis. J Pineal Res 43:121–129 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Yamamoto, S. et al. Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma. Clin Cancer Res 12:117–122 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Li, D. et al. Upregulation of nucleus HDGF predicts poor prognostic outcome in patients with penile squamous cell carcinoma bypass VEGF-A and Ki-67. Med Oncol 30:702 (2013).

    Article  PubMed  Google Scholar 

  42. Okuda, Y. et al. Hepatoma-derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor. Cancer Sci 94:1034–1041 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Trigona, W. L., Mullarky, I. K., Cao, Y. & Sordillo, L. M. Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells. Biochem J 394:207–216 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tanaka, T. et al. Redox regulation by thioredoxin superfamily; protection against oxidative stress and aging. Free Radic Res 33:851–855 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Zhang, D. et al. Synthesis an Molecular Recognition Studies on Small-Molecule Inhibitors for Thioredoxin Reductase. J Med Chem 57:8132–8139 (2014).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Science, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea

    Gun Woo Son, Hana Yang & Hye Rim Park

  2. Department of Microbiology, School of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea

    Seung Eun Lee, Cheung-Seog Park & Yong Seek Park

  3. Department of Physiology, School of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea

    Young-Ho Jin

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  1. Gun Woo Son
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Correspondence to Yong Seek Park.

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Son, G.W., Yang, H., Park, H.R. et al. Analysis of miRNA expression profiling in melatonin-exposured endothelial cells. Mol. Cell. Toxicol. 12, 73–81 (2016). https://doi.org/10.1007/s13273-016-0010-5

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  • DOI: https://doi.org/10.1007/s13273-016-0010-5

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