DOI QR코드

DOI QR Code

Profiling of Salivary Exosomal Micro RNAs in Burning Mouth Syndrome Patients

  • Kim, Kyun-Yo ;
  • Byun, Jin-Seok ;
  • Jung, Jae-Kwang ;
  • Choi, Jae-Kap
  • Received : 2019.03.05
  • Accepted : 2019.03.18
  • Published : 2019.03.30

Abstract

Purpose: The exact causes of burning mouth syndrome (BMS) is unclear so far. There are many studies to elucidate the relation between oral disease and genetic predisposition. In this study, we first tried to investigate salivary exosomal genetic components that could play an important role for diagnosing and elucidating the progression of BMS. Methods: We compared salivary exosomal micro RNAs (miRNAs) of BMS Patients to those of control using next generation sequencing (NGS). Unstimulated whole saliva from 15 patients with BMS and 10 control subjects were divided into two sets. Isolated exosomes and their total RNAs were subject to NGS for the screening of miRNAs. Results: There were up-regulated 10 exosomal miRNAs (hsa-miR-1273h-5p, hsa-miR-1273a, hsa-miR-1304-3p, hsa-miR-4449, hsa-miR-1285-3p, hsa-miR-6802-5p, hsa-miR-1268a, hsa-miR-1273d, hsa-miR-1273f, and hsa-miR-423-5p) and down-regulated 18 exosomal miRNAs (hsa-miR-27b-3p, hsa-miR-16-5p, hsa-miR-186-5p, hsa-miR-142-3p, hsa-miR-141-3p, hsa-miR-150-5p, hsa-miR-374a-5p, hsa-miR-93-5p, hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-148a-3p, hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-424-5p, hsa-miR-19b-3p, hsa-miR-99a-5p, hsa-miR-548d-3p, and hsa-miR-19a-3p) in BMS patients comparing with those of control subjects. Conclusions: We show that there are 28 differential expression of miRNAs between the patients with BMS and those of control subjects. The specific function of indicated miRNAs should be further elucidated.

Keywords

Burning mouth syndrome;miRNA;Mi-RNAs;Next generation sequencing

GGNGBC_2019_v44n1_25_f0001.png 이미지

Fig. 1. Representative diagram of small RNA composition in salivaryexosome.

GGNGBC_2019_v44n1_25_f0002.png 이미지

Fig. 2. Heatmap of exosomal miRNAs in the burning mouth syndrome patients and those of controls.

GGNGBC_2019_v44n1_25_f0003.png 이미지

Fig. 3. The lists of target miRNAs with (A) up-regulated and (B) down-regulated differential expression changes in comparison between burning mouth syndrome patients and those of controls.

References

  1. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia 2018;38:1-211.
  2. Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MDP. The prevalence of burning mouth syndrome: a population-based study. Br J Dermatol 2015;172:1654-1656. https://doi.org/10.1111/bjd.13613
  3. Scala A, Checchi L, Montevecchi M, Marini I, Giamberardino MA. Update on burning mouth syndrome: overview and patient management. Crit Rev Oral Biol Med 2003;14:275-291. https://doi.org/10.1177/154411130301400405
  4. Bergdahl M, Bergdahl J. Burning mouth syndrome: prevalence and associated factors. J Oral Pathol Med 1999;28:350-354.
  5. Muzyka BC, De Rossi SS. A review of burning mouth syndrome. Cutis 1999;64:29-35.
  6. Abetz LM, Savage NW. Burning mouth syndrome and psychological disorders. Aust Dent J 2009;54:84-93. https://doi.org/10.1111/j.1834-7819.2009.01099.x
  7. Hexel M, Sonneck G. Somatoform symptoms, anxiety, and depression in the context of traumatic life experiences by comparing participants with and without psychiatric diagnoses. Psychopathology 2002;35:303-312. https://doi.org/10.1159/000067066
  8. Woda A, Dao T, Gremeau-Richard C. Steroid dysregulation and stomatodynia (burning mouth syndrome). J Orofac Pain 2009;23:202-210.
  9. Lauria G, Majorana A, Borgna M, et al. Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome. Pain 2005;115:332-337. https://doi.org/10.1016/j.pain.2005.03.028
  10. Gremeau-Richard C, Woda A, Navez ML, et al. Topical clonazepam in stomatodynia: a randomised placebo-controlled study. Pain 2004;108:51-57. https://doi.org/10.1016/j.pain.2003.12.002
  11. Gao S, Wang Y, Wang Z. Assessment of trigeminal somatosensory evoked potentials in burning mouth syndrome. Chin J Dent Res 2000;3:40-46.
  12. Andersen HH, Duroux M, Gazerani P. MicroRNAs as modulators and biomarkers of inflammatory and neuropathic pain conditions. Neurobiol Dis 2014;71:159-168. https://doi.org/10.1016/j.nbd.2014.08.003
  13. Spielmann N, Wong DT. Saliva: diagnostics and therapeutic perspectives. Oral Dis 2011;17:345-354. https://doi.org/10.1111/j.1601-0825.2010.01773.x
  14. Ogawa Y, Taketomi Y, Murakami M, Tsujimoto M, Yanoshita R. Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing. Biol Pharm Bull 2013;36:66-75.
  15. Lee JM, Garon E, Wong DT. Salivary diagnostics. Orthod Craniofac Res 2009;12:206-211. https://doi.org/10.1111/j.1601-6343.2009.01454.x
  16. Han Y, Jia L, Zheng Y, Li W. Salivary exosomes: emerging roles in systemic disease. Int J Biol Sci 2018;14:633-643. https://doi.org/10.7150/ijbs.25018
  17. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-659. https://doi.org/10.1038/ncb1596
  18. Sarko DK, McKinney CE. Exosomes: origins and therapeutic potential for neurodegenerative disease. Front Neurosci 2017;11:82.
  19. Orlova IA, Alexander GM, Qureshi RA, et al. MicroRNA modulation in complex regional pain syndrome. J Transl Med 2011;9:195. https://doi.org/10.1186/1479-5876-9-195
  20. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001;294:853-858. https://doi.org/10.1126/science.1064921
  21. Huang X, Yuan T, Tschannen M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 2013;14:319. https://doi.org/10.1186/1471-2164-14-319
  22. Michael A, Bajracharya SD, Yuen PS, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 2010;16:34-38. https://doi.org/10.1111/j.1601-0825.2009.01604.x
  23. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136:215-233. https://doi.org/10.1016/j.cell.2009.01.002
  24. Wu Y, Xu J, Xu J, et al. Lower serum levels of miR-29c-3p and miR-19b-3p as biomarkers for Alzheimer's disease. Tohoku J Exp Med 2017;242:129-136. https://doi.org/10.1620/tjem.242.129
  25. Mandolesi G, De Vito F, Musella A, et al. miR-142-3p is a key regulator of IL-$1{\beta}$-dependent synaptopathy in neuroinflammation. J Neurosci 2017;37:546-561. https://doi.org/10.1523/JNEUROSCI.0851-16.2016
  26. Bai G, Ambalavanar R, Wei D, Dessem D. Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain. Mol Pain 2007;3:15.
  27. Dunaeva M, Blom J, Thurlings R, Pruijn GJM. Circulating serum miR-223-3p and miR-16-5p as possible biomarkers of early rheumatoid arthritis. Clin Exp Immunol 2018;193:376-385. https://doi.org/10.1111/cei.13156
  28. Qu Y, Liu H, Lv X, et al. MicroRNA-16-5p overexpression suppresses proliferation and invasion as well as triggers apoptosis by targeting VEGFA expression in breast carcinoma. Oncotarget 2017;8:72400-72410.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)