DOI QR코드

DOI QR Code

Differential expression of microRNAs in the saliva of patients with aggressive periodontitis: a pilot study of potential biomarkers for aggressive periodontitis

  • Lee, Nam-Hun (Department of Periodontics, Asan Medical Center) ;
  • Lee, Eunhye (Department of Conservative Dentistry, School of Dentistry, Seoul National University) ;
  • Kim, Young-Sung (Department of Periodontics, Asan Medical Center) ;
  • Kim, Won-Kyung (Department of Periodontics, Asan Medical Center) ;
  • Lee, Young-Kyoo (Department of Periodontics, Asan Medical Center) ;
  • Kim, Su-Hwan (Department of Periodontics, Asan Medical Center)
  • Received : 2019.12.30
  • Accepted : 2020.07.06
  • Published : 2020.10.30

Abstract

Purpose: The aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients. Methods: PCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB. Results: Four downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function. Conclusions: This study is the first analysis of miRNAs in the saliva of patients with AP. Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.

Keywords

References

  1. Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011;12:99-110. https://doi.org/10.1038/nrg2936
  2. Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 2012;13:271-82. https://doi.org/10.1038/nrg3162
  3. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-97. https://doi.org/10.1016/S0092-8674(04)00045-5
  4. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 2008;455:58-63. https://doi.org/10.1038/nature07228
  5. Irwandi RA, Vacharaksa A. The role of microRNA in periodontal tissue: a review of the literature. Arch Oral Biol 2016;72:66-74. https://doi.org/10.1016/j.archoralbio.2016.08.014
  6. Kim SH, Lee SY, Lee YM, Lee YK. MicroRNAs as biomarkers for dental diseases. Singapore Dent J 2015;36:18-22. https://doi.org/10.1016/j.sdj.2015.09.001
  7. Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol 2012;9:742-50. https://doi.org/10.4161/rna.20018
  8. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 2009;32:189-94. https://doi.org/10.1016/j.jaut.2009.02.012
  9. Alexander M, O'Connell RM. Noncoding RNAs and chronic inflammation: micro-managing the fire within. BioEssays 2015;37:1005-15. https://doi.org/10.1002/bies.201500054
  10. Romaine SP, Tomaszewski M, Condorelli G, Samani NJ. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart 2015;101:921-8. https://doi.org/10.1136/heartjnl-2013-305402
  11. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther 2016;1:15004. https://doi.org/10.1038/sigtrans.2015.4
  12. Luan X, Zhou X, Naqvi A, Francis M, Foyle D, Nares S, et al. MicroRNAs and immunity in periodontal health and disease. Int J Oral Sci 2018;10:24. https://doi.org/10.1038/s41368-018-0025-y
  13. Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol 2016;231:25-30. https://doi.org/10.1002/jcp.25056
  14. Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 2010;391:73-7. https://doi.org/10.1016/j.bbrc.2009.11.005
  15. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105:10513-8. https://doi.org/10.1073/pnas.0804549105
  16. Xie Z, Yin X, Gong B, Nie W, Wu B, Zhang X, et al. Salivary microRNAs show potential as a noninvasive biomarker for detecting resectable pancreatic cancer. Cancer Prev Res (Phila) 2015;8:165-73. https://doi.org/10.1158/1940-6207.CAPR-14-0192
  17. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 2009;15:5473-7. https://doi.org/10.1158/1078-0432.CCR-09-0736
  18. Alevizos I, Alexander S, Turner RJ, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjogren's syndrome. Arthritis Rheum 2011;63:535-44.
  19. Xie ZJ, Chen G, Zhang XC, Li DF, Huang J, Li ZJ. Saliva supernatant miR-21: a novel potential biomarker for esophageal cancer detection. Asian Pac J Cancer Prev 2012;13:6145-9. https://doi.org/10.7314/APJCP.2012.13.12.6145
  20. Xie YF, Shu R, Jiang SY, Liu DL, Zhang XL. Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int J Oral Sci 2011;3:125-34. https://doi.org/10.4248/IJOS11046
  21. Stoecklin-Wasmer C, Guarnieri P, Celenti R, Demmer RT, Kebschull M, Papapanou PN. MicroRNAs and their target genes in gingival tissues. J Dent Res 2012;91:934-40. https://doi.org/10.1177/0022034512456551
  22. Ogata Y, Matsui S, Kato A, Zhou L, Nakayama Y, Takai H. MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients. J Oral Sci 2014;56:253-60. https://doi.org/10.2334/josnusd.56.253
  23. Lee YH, Na HS, Jeong SY, Jeong SH, Park HR, Chung J. Comparison of inflammatory microRNA expression in healthy and periodontitis tissues. Biocell 2011;35:43-9. https://doi.org/10.32604/biocell.2011.35.043
  24. Perri R, Nares S, Zhang S, Barros SP, Offenbacher S. MicroRNA modulation in obesity and periodontitis. J Dent Res 2012;91:33-8. https://doi.org/10.1177/0022034511425045
  25. Na HS, Park MH, Song YR, Kim S, Kim HJ, Lee JY, et al. Elevated microRNA-128 in periodontitis mitigates tumor necrosis factor-${\alpha}$ response via p38 signaling pathway in macrophages. J Periodontol 2016;87:e173-82. https://doi.org/10.1902/jop.2016.160033
  26. Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A, Bentwich I, et al. MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 2004;14:2486-94. https://doi.org/10.1101/gr.2845604
  27. Chen Y, Gelfond JA, McManus LM, Shireman PK. Reproducibility of quantitative RT-PCR array in miRNA expression profiling and comparison with microarray analysis. BMC Genomics 2009;10:407. https://doi.org/10.1186/1471-2164-10-407
  28. Mestdagh P, Feys T, Bernard N, Guenther S, Chen C, Speleman F, et al. High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA. Nucleic Acids Res 2008;36:e143. https://doi.org/10.1093/nar/gkn725
  29. Fujimori K, Yoneda T, Tomofuji T, Ekuni D, Azuma T, Maruyama T, et al. Detection of salivary miRNAs reflecting chronic periodontitis: a pilot study. Molecules 2019;24:1034. https://doi.org/10.3390/molecules24061034
  30. Van der Velden U. What exactly distinguishes aggressive from chronic periodontitis: is it mainly a difference in the degree of bacterial invasiveness? Periodontol 2000 2017;75:24-44. https://doi.org/10.1111/prd.12202
  31. Amaral SA, Pereira TS, Brito JA, Cortelli SC, Cortelli JR, Gomez RS, et al. Comparison of miRNA expression profiles in individuals with chronic or aggressive periodontitis. Oral Dis 2019;25:561-8. https://doi.org/10.1111/odi.12994
  32. Ghotloo S, Motedayyen H, Amani D, Saffari M, Sattari M. Assessment of microRNA-146a in generalized aggressive periodontitis and its association with disease severity. J Periodontal Res 2019;54:27-32. https://doi.org/10.1111/jre.12538
  33. Lang N, Bartold PM, Cullinan M, Jeffcoat M, Mombelli A, Murakami S, et al. Consensus report: aggressive periodontitis. Ann Periodontol 1999;4:53. https://doi.org/10.1902/annals.1999.4.1.53
  34. Yoshizawa JM, Wong DT. Salivary microRNAs and oral cancer detection. Methods Mol Biol 2013;936:313-24. https://doi.org/10.1007/978-1-62703-083-0_24
  35. Li J, Han X, Wan Y, Zhang S, Zhao Y, Fan R, et al. TAM 2.0: tool for MicroRNA set analysis. Nucleic Acids Res 2018;46:W180-5. https://doi.org/10.1093/nar/gky509
  36. Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res 2018;46:D296-302. https://doi.org/10.1093/nar/gkx1067
  37. Kamburov A, Stelzl U, Lehrach H, Herwig R. The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res 2013;41:D793-800. https://doi.org/10.1093/nar/gks1055
  38. TAB2: TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [Homo sapiens (human)] [Internet]. Bethesda (MD): National Center for Biotechnology Information; 2019 [cited 2019 Sep 1]. Available from: https://www.ncbi.nlm.nih.gov/gene/23118.

Cited by

  1. Quantification of Bacteria in Mouth-Rinsing Solution for the Diagnosis of Periodontal Disease vol.10, pp.4, 2020, https://doi.org/10.3390/jcm10040891