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Circular RNA in Saliva

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Circular RNAs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1087))

Abstract

Although the type and amount of salivary components are influenced by many factors, due to easy, quick, cheap, and noninvasive sampling method alongside with the existence of the vast majority of the substances found in peripheral blood and urine in it, in recent years saliva has been considered as an ideal biofluid for disease research. Salivary circular RNA (circRNA), as an endogenous RNA molecule with a great variety of regulatory potency, is becoming a novel focus for detecting wide range of local or systemic diseases. Expectantly, with characterization of many more circRNAs in saliva, their motifs, and target sites, they can be used routinely in personalized medicine.

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References

  1. Garrett JR (1975) Changing attitudes on salivary secretion—a short history on spit. Proc R Soc Med 68:553–560

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Schipper RG, Silletti E, Vingerhoeds MH (2007) Saliva as research material: biochemical, physicochemical and practical aspects. Arch Oral Biol 52:1114–1135

    Article  CAS  PubMed  Google Scholar 

  3. Farnaud SJ, Kosti O, Getting SJ et al (2010) Saliva: physiology and diagnostic potential in health and disease. Sci World J 10(16):434–456

    Article  CAS  Google Scholar 

  4. Malathi N, Mythili S, Vasanthi HR (2014) Salivary diagnostics: a brief review. ISRN Dent 2014:158786

    PubMed  PubMed Central  Google Scholar 

  5. Khurshid Z, Naseem M, Sheikh Z et al (2016) Oral antimicrobial peptides: types and role in the oral cavity. Saudi Pharm J 24(5):515–524

    Article  PubMed  Google Scholar 

  6. Hofman LF (2001) Human saliva as a diagnostic specimen. J Nutr 131:1621S–1625S

    Article  CAS  PubMed  Google Scholar 

  7. Llena-Puy C (2006) The rôle of saliva in maintaining oral health and as an aid to diagnosis. Med Oral Patol Oral Cir Bucal 11(5):E449–E455

    PubMed  Google Scholar 

  8. Lawrence HP (2002) Salivary markers of systemic disease: noninvasive diagnosis of disease and monitoring of general health. J Can Dent Assoc 68(3):170–174

    PubMed  Google Scholar 

  9. Almstahl A, Wikstrom M (2003) Electrolytes in stimulated whole saliva in individuals with hyposalivation of different origins. Arch Oral Biol 48:337–344

    Article  CAS  PubMed  Google Scholar 

  10. Aps JK, Martens LC (2005) Review: the physiology of saliva and transfer of drugs into saliva. Forensic Sci Int 150:119–131

    Article  CAS  PubMed  Google Scholar 

  11. Haeckel R, Hanecke P (1996) Application of saliva for drug monitoring: an in vivo model for transmembrane transport. Eur J Clin Chem Clin Biochem 34:171–191

    CAS  PubMed  Google Scholar 

  12. Forde M, Koka S, Ecker S et al (2006) Systemic assessments utilizing saliva, part I: general considerations and current assessments. Int J Prosthodont 19:43–52

    PubMed  Google Scholar 

  13. Lee YH, Wong DT (2009) Saliva: an emerging biofluid for early detection of diseases. Am J Dent 22(4):241–248

    PubMed  PubMed Central  Google Scholar 

  14. Humphrey SP, Williamson RT (2001) A review of saliva: normal composition, flow, and function. J Prosthet Dent 85:162–169

    Article  CAS  PubMed  Google Scholar 

  15. Aps JK, Van Den Maagdenberg K, Delanghe JR et al (2002) Flow cytometry as a new method to quantify the cellular content of human saliva and its relation to gingivitis. Clin Chim Acta 321:35–41

    Article  CAS  PubMed  Google Scholar 

  16. Falcão DP, da Mota LM, Pires AL et al (2013) Sialometry: aspects of clinical interest. Rev Bras Reumatol 53(6):525–531

    Article  PubMed  Google Scholar 

  17. Carpenter GH (2013) The secretion, components, and properties of saliva. Annu Rev Food Sci Technol 4:267–276

    Article  CAS  PubMed  Google Scholar 

  18. Ben-Aryeh H, Fisher M, Szargel R et al (1990) Composition of whole unstimulated saliva of healthy children: changes with age. Arch Oral Biol 35:929–931

    Article  CAS  PubMed  Google Scholar 

  19. Salvolini E, Mazzanti L, Martarelli D et al (1999) Changes in the composition of human unstimulated whole saliva with age. Aging 11:119–122

    CAS  PubMed  Google Scholar 

  20. Nuriel-Ohayon M, Neuman H, Koren O (2016) Microbial changes during pregnancy, birth, and infancy. Front Microbiol 7:1031

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hassaneen M, Maron JL (2017) Salivary diagnostics in pediatrics: applicability, translatability, and limitations. Front Public Health 20(5):83

    Article  Google Scholar 

  22. Vandewoestyne M, Van Hoofstat D, Franssen A et al (2013) Presence and potential of cell free DNA in different types of forensic samples. Forensic Sci Int Genet 7:316–320

    Article  CAS  PubMed  Google Scholar 

  23. Tu M, Wei F, Yang J et al (2015) Detection of exosomal biomarker by electric field-induced release and measurement (ERIFM). J Vis Exp 95:52439

    Google Scholar 

  24. Yao W, Mei C, Nan X et al (2016) Evaluation and comparison of in vitro degradation kinetics of DNA in serum, urine and saliva: a qualitative study. Gene 15:142–148

    Article  Google Scholar 

  25. Spielmann N, Ilsley D, Gu J et al (2012) The human salivary RNA transcriptome revealed by massively parallel sequencing. Clin Chem 58:1314–1321

    Article  CAS  PubMed  Google Scholar 

  26. Brosnan CA, Voinnet O (2009) The long and the short of noncoding RNAs. Curr Opin Cell Biol 21:416–425

    Article  CAS  PubMed  Google Scholar 

  27. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874

    Article  CAS  PubMed  Google Scholar 

  28. Lasda E, Parker R (2014) Circular RNAs: diversity of form and function. RNA 20:1829–1842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li Y, St John MA, Zhou X et al (2004) Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 10:8442–8450

    Article  CAS  PubMed  Google Scholar 

  30. Dalmay T (2008) MicroRNAs and cancer. J Intern Med 263:366–375

    Article  CAS  PubMed  Google Scholar 

  31. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  CAS  PubMed  Google Scholar 

  32. Reis EM, Verjovski-Almeida S (2012) Perspectives of long non-coding RNAs in cancer diagnostics. Front Genet 3:32

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Tang H, Wu Z, Zhang J et al (2013) Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis. Mol Med Rep 7:761–766

    Article  CAS  PubMed  Google Scholar 

  34. Jafari Ghods F, Topal Sarikaya A, Arda N et al (2017) MiRNA and mRNA profiling in systemic lupus reveals a novel set of cytokine – related miRNAs and their target genes in cases with and without renal involvement. Kidney Blood Press Res 42(6):1322–1337

    Article  CAS  PubMed  Google Scholar 

  35. Delima AJ, Van Dyke TE (2003) Origin and function of the cellular components in gingival crevice fluid. Periodontol 2000 31:55–76

    Article  PubMed  Google Scholar 

  36. Kaufman E, Lamster IB (2002) The diagnostic applications of saliva—a review. Crit Rev Oral Biol Med 13:197–212

    Article  PubMed  Google Scholar 

  37. Streckfus CF, Bigler L, Dellinger T et al (2004) The expression of the c-erbB-2 receptor protein in glandular salivary secretions. J Oral Pathol Med 33:595–600

    Article  CAS  PubMed  Google Scholar 

  38. Fabian TK, Fejerdy P, Csermely P (2008) Salivary genomics, transcriptomics, and proteomics: the emerging concept of the oral ecosystem and their use in the early diagnosis of cancer and other diseases. Curr Genomics 9:11–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Parahitiyawa NB, Scully C, Leung WK et al (2010) Exploring the oral bacterial flora: current status and future directions. Oral Dis 16:136–145

    Article  CAS  PubMed  Google Scholar 

  40. Lif Holgerson P, Öhman C, Rönnlund A et al (2015) Maturation of oral microbiota in children with or without dental caries. PLoS One 10:e0128534

    Article  PubMed  PubMed Central  Google Scholar 

  41. Li Y, Zhou X, St John MA et al (2004) RNA profiling of cell-free saliva using microarray technology. J Dent Res 83:199–203

    Article  CAS  PubMed  Google Scholar 

  42. Meyer S, Temme C, Wahle E (2004) Messenger RNA turnover in eukaryotes: pathways and enzymes. Crit Rev Biochem Mol Biol 39:197–216

    Article  CAS  PubMed  Google Scholar 

  43. Wong BC, Chiu RW, Tsui NB et al (2005) Circulating placental RNA in maternal plasma is associated with a preponderance of 5mRNA fragments: implications for noninvasive prenatal diagnosis and monitoring. Clin Chem 51:1786–1795

    Article  CAS  PubMed  Google Scholar 

  44. Park NJ, Li Y, Yu T et al (2006) Characterization of RNA in saliva. Clin Chem 52(6):988–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lamblin G, Degroote S, Perini JM et al (2001) Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis. Glycoconj J 18:661–684

    Article  CAS  PubMed  Google Scholar 

  46. Turchinovich A, Weiz L, Langheinz A et al (2011) Characterization of extracellular circulating microRNA. Nucleic Acids Res 39:7223–7233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  CAS  PubMed  Google Scholar 

  48. Michael A, Bajracharya SD, Yuen PS et al (2010) Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 16:34–38

    Article  CAS  PubMed  Google Scholar 

  49. Koga Y, Yasunaga M, Moriya Y et al (2011) Exosome can prevent RNase from degrading microRNA in feces. J Gastrointest Oncol 2:215–222

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Gallo A, Tandon M, Alevizos I et al (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7:e30679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ogawa Y, Taketomi Y, Murakami M et al (2013) Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing. Biol Pharm Bull 36:66–75

    Article  CAS  PubMed  Google Scholar 

  52. Ogawa Y, Miura Y, Harazono A et al (2011) Proteomic analysis of two types of exosomes in human whole saliva. Biol Pharm Bull 34:13–23

    Article  CAS  PubMed  Google Scholar 

  53. Wong DT (2012) Salivaomics. J Am Dent Assoc 143:19S–24S

    Article  PubMed  Google Scholar 

  54. Ramachandran P, Boontheung P, Xie Y et al (2006) Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. J. Proteome Res 5:1493–1503

    Article  CAS  Google Scholar 

  55. Park NJ, Zhou X, Yu T et al (2007) Characterization of salivary RNA by cDNA library analysis. Arch Oral Biol 52:30–35

    Article  CAS  PubMed  Google Scholar 

  56. Whitelegge JP, Zabrouskov V, Halgand F et al (2007) Protein-sequence polymorphisms and post-translational modifications in proteins from human saliva using top–down fourier-transform ion cyclotron resonance mass spectrometry. Int J Mass Spectrom 268:190–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hu Z, Zimmermann BG, Zhou H et al (2008) Exon-level expression profiling: a comprehensive transcriptome analysis of oral fluids. Clin Chem 54:824–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wei F, Wang J, Liao W et al (2008) Electrochemical detection of low-copy number salivary RNA based on specific signal amplification with a hairpin probe. Nucleic Acids Res 36:e65

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sondej M, Denny PA, Xie Y et al (2009) Glycoprofiling of the human salivary proteome. Clin Proteomics 5:52–68

    Article  CAS  PubMed  Google Scholar 

  60. Hu S, Jiang J, Wong DT (2010) Proteomic analysis of saliva: 2D gel electrophoresis, LC–MS/MS, and western blotting. Methods Mol Biol 666:31–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Oshlack A, Robinson MD, Young MD (2010) From RNA-seq reads to differential expression results. Genome Biol 11:220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mandel ID (1993) Salivary diagnosis: promises, promises. Ann N Y Acad Sci 694:1–10

    Article  CAS  PubMed  Google Scholar 

  63. Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K et al (2017) Saliva diagnostics – current views and directions. Exp Biol Med (Maywood) 242(5):459–472

    Article  CAS  Google Scholar 

  64. Miller SM (1994) Saliva testing--a non-traditional diagnostic tool. Clin Lab Sci 7(1):39–44

    CAS  PubMed  Google Scholar 

  65. Majem B, Rigau M, Reventós J, et al (2015) Non-coding RNAs in saliva: emerging biomarkers for molecular diagnostics. Farah CS, ed. Int J Mol Sci 16(4):8676–8698

    Google Scholar 

  66. Lee YH, Kim JH, Zhou H et al (2012) Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma. J Mol Med (Berl) 90:427–434

    Article  CAS  Google Scholar 

  67. Zhang L, Xiao H, Karlan S et al (2010) Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the noninvasive detection of breast cancer. PLoS One 5:e15573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hu S, Wang J, Meijer J et al (2007) Salivary proteomic and genomic biomarkers for primary Sjogren’s syndrome. Arthritis Rheum 56:3588–3600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li Y, Zheng Q, Bao C et al (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25(8):981–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32(5):453–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yang L, Duff MO, Graveley BR et al (2011) Genomewide characterization of non-polyadenylated RNAs. Genome Biol 12(2):R16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Memczak S, Papavasileiou P, Peters O et al (2015) Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One 10(10):e0141214

    Article  PubMed  PubMed Central  Google Scholar 

  73. Enuka Y, Lauriola M, Feldman ME et al (2016) Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res 44(3):1370–1383

    Article  CAS  PubMed  Google Scholar 

  74. Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    Article  CAS  PubMed  Google Scholar 

  75. Wang Y, Wang Z (2015) Efficient back splicing produces translatable circular mRNAs. RNA 21:172–179

    Article  PubMed  PubMed Central  Google Scholar 

  76. Xie H, Ren X, Xin S et al (2016) Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer. Oncotarget 7(18):26680–26691

    PubMed  PubMed Central  Google Scholar 

  77. Zhu M, Xu Y, Chen Y et al (2017) Circular BANP, an up-regulated circular RNA that modulates cell proliferation in colorectal cancer. Biomed Pharmacother 88:138–144

    Article  CAS  PubMed  Google Scholar 

  78. Zhang YG, Yang HL, Long Y, Li WL (2016) Circular RNA in blood corpuscles combined with plasma protein factor for early prediction of pre-eclampsia. BJOG 123:2113. https://doi.org/10.1111/1471-0528.13897

    Article  CAS  PubMed  Google Scholar 

  79. Zhao Z, Li X, Gao C et al (2017) Peripheral blood circular RNA hsa_circ_0124644 can be used as a diagnostic biomarker of coronary artery disease. Sci Rep 7:39918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Panda AC, Grammatikakis I, Kim KM et al (2017) Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res 45(7):4021–4035

    Article  CAS  PubMed  Google Scholar 

  81. Li H, Hao X, Wang H et al (2016) Circular RNA expression profile of pancreatic ductal adenocarcinoma revealed by microarray. Cell Physiol Biochem 40(6):1334–1344

    Article  CAS  PubMed  Google Scholar 

  82. Li P, Chen S, Chen H et al (2015) Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta 444:132–136

    Article  CAS  PubMed  Google Scholar 

  83. Du WW, Yang W, Chen Y et al (2017) Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 38:1402–1412

    Article  PubMed  Google Scholar 

  84. Vausort M, Salgado-Somoza A, Zhang L et al (2016) Myocardial infarction-associated circular RNA predicting left ventricular dysfunction. J Am Coll Cardiol 68:1247–1248

    Article  PubMed  Google Scholar 

  85. Cao S, Wei D, Li X et al (2017) Novel circular RNA expression profiles reflect progression of patients with hypopharyngeal squamous cell carcinoma. Oncotarget 8(28):45367–45379

    Article  PubMed  PubMed Central  Google Scholar 

  86. Ouyang Q, Wu J, Jiang Z et al (2017) Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from rheumatoid arthritis patients. Cell Physiol Biochem 42(2):651–659

    Article  CAS  PubMed  Google Scholar 

  87. Li H, Li K, Lai W et al (2018) Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus. Clin Chim Acta 480:17–25

    Article  CAS  PubMed  Google Scholar 

  88. Wang YH, Yu XH, Luo SH et al (2015) Comprehensive circular RNA profiling reveals that circularRNA100783 is involved in chronic CD28-associated CD8(+) T cell ageing. Immun Ageing 12:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Turner-Cobb JM, Rixon L, Jessop DS (2008) A prospective study of diurnal cortisol responses to the social experience of school transition in four-year-old children: anticipation, exposure, and adaptation. Dev Psychobiol 50:377–389

    Article  PubMed  Google Scholar 

  90. Bahn JH, Zhang Q, Li F et al (2015) The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem 61(1):221–230

    Article  CAS  PubMed  Google Scholar 

  91. Suzuki H, Zuo Y, Wang J et al (2006) Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res 34:e63

    Article  PubMed  PubMed Central  Google Scholar 

  92. Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Cortés-López M, Gruner MR, Cooper DA et al (2018) Global accumulation of circRNAs during aging in Caenorhabditis elegans. BMC Genomics 19(1):8

    Article  PubMed  PubMed Central  Google Scholar 

  94. Abu N, Jamal R (2016) Circular RNAs as promising biomarkers: a mini-review. Front Physiol 7:355

    Article  PubMed  PubMed Central  Google Scholar 

  95. Greene J, Baird AM, Brady L et al (2017) Circular RNAs: biogenesis, function and role in human diseases. Front Mol Biosci 4:38

    Article  PubMed  PubMed Central  Google Scholar 

  96. Barrett SP, Salzman J (2016) Circular RNAs: analysis, expression and potential functions. Development 143(11):1838–1847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chen I, Chen CY, Chuang TJ (2015) Biogenesis, identification, and function of exonic circular RNAs. WIREs RNA 6:563–579

    Article  CAS  PubMed  Google Scholar 

  98. Hansen TB, Venø MT, Damgaard CK et al (2016) Comparison of circular RNA prediction tools. Nucleic Acids Res 44(6):e58

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Prof. Dr. Ahad Jafari Ghods, MD., FACP, (Iran University of Medical Sciences) for critical reading and comments on the manuscript.

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The author declares no competing financial interests.

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Jafari Ghods, F. (2018). Circular RNA in Saliva. In: Xiao, J. (eds) Circular RNAs. Advances in Experimental Medicine and Biology, vol 1087. Springer, Singapore. https://doi.org/10.1007/978-981-13-1426-1_11

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