Skip to main content
SpringerLink
Log in

Emerging Role of Circular RNAs as Potential Biomarkers for the Diagnosis of Human Diseases

  • Chapter
  • First Online:
Circular RNAs

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

Abstract

In the eukaryotic transcriptome, the evolutionary conserved circular RNAs naturally occur from the family of noncoding RNAs. Circular RNAs possess a unique feature to interact with nucleic acids and ribonucleoproteins and are establishing themselves as an obligatory composition for the regulatory messages which are encoded by the genome. The back-splicing mechanism leads to the formation of circularized RNA, and because of this they become resistant to exonuclease-mediated degradation. The differential and aberrant expression of circular RNAs can be detected with the help of various profiling methods by using serum, plasma, and tissue samples. In this chapter, we have highlighted the role of circular RNAs as putative biomarker for the detection of various human diseases along with its profiling methods. Here we have discussed the differentially expressed circular RNAs in neurological disorders and infectious diseases along with cancer diseases. For instance, in case of pulmonary tuberculosis, hsa_circRNA_001937 was upregulated, while hsa_circRNA_102101 got downregulated; Hsa_circ_000178 was depicted to get upregulated in breast cancer which is associated with disease progression. Furthermore, it has been observed that circRNAs are abundantly present within the mammalian brain tissues. In epileptic condition, Circ-EFCAB2 was observed to get notably upregulated within patients. Taking the above conditions into consideration, circular RNAs have proven themselves as promising noninvasive biomarker for the detection of human diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhi-Chun Z, Xiao-Long G, Li X (2017) The novel roles of circular RNAs in metabolic organs. Genes Dis 5(1):16–23

    Google Scholar 

  2. Chen Y, Li C, Tan C et al (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53(6):359–365

    Article  CAS  PubMed  Google Scholar 

  3. 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 

  4. Carriero S, Damha MJ (2003) Template-mediated synthesis of lariat RNA and DNA. J Org Chem 68(22):8328–8338

    Article  CAS  PubMed  Google Scholar 

  5. Li J, Yang J, Zhou P et al (2015) Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res 5(2):472

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Lasda E, Parker R (2016) Circular RNAs co-precipitate with extracellular vesicles: a possible mechanism for circRNA clearance. PLoS One 11(2):e0148407

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li WH, Song YC, Zhang H (2017) Decreased expression of Hsa_circ_00001649 in gastric cancer and its clinical significance. Dis Markers 2017:4587698

    PubMed  PubMed Central  Google Scholar 

  9. Ebert MS, Sharp PA (2010) MicroRNA sponges: progress and possibilities. RNA 16(11):2043–2050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rybak-Wolf A, Stottmeister C, Glažar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Memczak S, Jens M, Elefsinioti A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333

    Article  CAS  PubMed  Google Scholar 

  13. Jost I, Shalamova LA, Gerresheim GK et al (2018) Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges. RNA Biol 28:1–8

    Article  Google Scholar 

  14. Panda AC, De S, Grammatikakis I et al (2017) High-purity circular RNA isolation method (RPAD) reveals vast collection of intronic circRNAs. Nucleic Acids Res 45(12):e116–e116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Voelkerding KV, Dames SA, Durtschi JD (2009) Next-generation sequencing: from basic research to diagnostics. Clin Chem 55(4):641–658

    Article  CAS  PubMed  Google Scholar 

  16. Chen L, Yu Y, Zhang X et al (2016) PcircRNA_finder: a software for circRNA prediction in plants. Bioinformatics 32(22):3528–3529

    CAS  PubMed  PubMed Central  Google Scholar 

  17. World Health Organization (2016) Global tuberculosis report 2016. World Health Organization, Geneva

    Google Scholar 

  18. Lü L, Sun J, Shi P et al (2017) Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer. Oncotarget 8(27):44096

    PubMed  PubMed Central  Google Scholar 

  19. Du WW, Fang L, Yang W et al (2017) Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ 24(2):357

    Article  CAS  PubMed  Google Scholar 

  20. Du WW, Yang W, Liu E et al (2016) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44(6):2846–2858

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bachmayr-Heyda A, Reiner AT, Auer K et al (2015) Correlation of circular RNA abundance with proliferation–exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep 5:8057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Qian Z, Liu H, Li M et al (2018) Potential diagnostic power of blood circular RNA expression in active pulmonary tuberculosis. EBioMedicine 27:18–26

    Article  PubMed  Google Scholar 

  23. Huang Z-K, Yao F-Y, Xu J-Q et al (2018) Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from active tuberculosis patients. Cell Physiol Biochem 45(3):1230–1240

    Article  CAS  PubMed  Google Scholar 

  24. Zhu RX, Seto W-K, Lai C-L et al (2016) Epidemiology of hepatocellular carcinoma in the Asia-Pacific region. Gut Liver 10(3):332–339

    Article  PubMed  PubMed Central  Google Scholar 

  25. Beasley RP (1988) Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61(10):1942–1956

    Article  CAS  PubMed  Google Scholar 

  26. Custer B, Sullivan SD, Hazlet TK et al (2004) Global epidemiology of hepatitis B virus. J Clin Gastroenterol 38(10):S158–S168

    Article  PubMed  Google Scholar 

  27. Yu L, Gong X, Sun L et al (2016) The circular RNA Cdr1as act as an oncogene in hepatocellular carcinoma through targeting miR-7 expression. PLoS One 11(7):e0158347

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fu L, Yao T, Chen Q et al (2017) Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma. Oncotarget 8(35):58405

    PubMed  PubMed Central  Google Scholar 

  29. McKillop IH, Moran DM, Jin X et al (2006) Molecular pathogenesis of hepatocellular carcinoma. J Surg Res 136(1):125–135

    Article  CAS  PubMed  Google Scholar 

  30. Wu K, House L, Liu W et al (2012) Personalized targeted therapy for lung cancer. Int J Mol Sci 13(9):11471–11496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ma PC (2012) Personalized targeted therapy in advanced non-small cell lung cancer. Cleve Clin J Med 79:eS56–eS60

    Article  PubMed  Google Scholar 

  32. Zhang S, Zeng X, Ding T et al (2018) Microarray profile of circular RNAs identifies hsa_circ_0014130 as a new circular RNA biomarker in non-small cell lung cancer. Sci Rep 8(1):2878

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wan L, Zhang L, Fan K et al (2016) Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/β-catenin pathway. Biomed Res Int 2016(1):1579490

    PubMed  PubMed Central  Google Scholar 

  34. Yao J-T, Zhao S-H, Liu Q-P et al (2017) Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value. Pathol Res Pract 213(5):453–456

    Article  CAS  PubMed  Google Scholar 

  35. Luo Y-H, Zhu X-Z, Huang K-W et al (2017) Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and metastasis of lung cancer. Biomed Pharmacother 96:892–898

    Article  CAS  PubMed  Google Scholar 

  36. Zhu X, Wang X, Wei S et al (2017) hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J 284(14):2170–2182

    Article  CAS  PubMed  Google Scholar 

  37. Zhang Y, Zhao H, Zhang L (2018) Identification of the tumor-suppressive function of circular RNA FOXO3 in non-small cell lung cancer through sponging miR-155. Mol Med Rep 17(6):7692–7700

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Ji W, Qiu C, Wang M et al (2018) Hsa_circ_0001649: a circular RNA and potential novel biomarker for colorectal cancer. Biochem Biophys Res Commun 497(1):122–126

    Article  CAS  PubMed  Google Scholar 

  39. Yin WB, Yan MG, Fang X, et al (2017) Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection. Clin Chim Acta. https://doi.org/10.1016/j.cca.2017.10.011

  40. Cocquerelle C, Mascrez B, Hetuin D et al (1993) Mis-splicing yields circular RNA molecules. FASEB J 7(1):155–160

    Article  CAS  PubMed  Google Scholar 

  41. Siegel RL, Sahar L, Portier KM et al (2015) Cancer death rates in US congressional districts. CA Cancer J Clin 65(5):339–344

    Article  PubMed  Google Scholar 

  42. Boleij A, van Gelder MM, Swinkels DW et al (2011) Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis. Clin Infect Dis 53(9):870–878

    Article  CAS  PubMed  Google Scholar 

  43. 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

    PubMed  PubMed Central  Google Scholar 

  44. Weng W, Wei Q, Toden S et al (2017) Circular RNA ciRS-7—a promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin Cancer Res 23(14):3918–3928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang X, Zhang Y, Huang L et al (2015) Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances. Int J Clin Exp Pathol 8(12):16020

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang P, Zuo Z, Shang W et al (2017) Identification of differentially expressed circular RNAs in human colorectal cancer. Tumor Biol 39(3):1010428317694546

    Google Scholar 

  47. Zhang Y, Zhang Y, Li X et al (2017) Microarray analysis of circular RNA expression patterns in polarized macrophages. Int J Mol Med 39(2):373–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Huang G, Zhu H, Shi Y et al (2015) cir-ITCH plays an inhibitory role in colorectal cancer by regulating the Wnt/β-catenin pathway. PLoS One 10(6):e0131225

    Article  PubMed  PubMed Central  Google Scholar 

  49. Huang J-L, Qin M-C, Zhou Y et al (2018) Comprehensive analysis of differentially expressed profiles of Alzheimer’s disease associated circular RNAs in an Alzheimer’s disease mouse model. Aging (Albany NY) 10(2):253

    Google Scholar 

  50. Mo D (2018) The role of Aβ circRNA in Alzheimer’s disease. bioRxiv:260968

    Google Scholar 

  51. Burmistrova O, Goltsov A, Abramova L et al (2007) MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11). Biochem Mosc 72(5):578–582

    Article  CAS  Google Scholar 

  52. Cogswell JP, Ward J, Taylor IA et al (2008) Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14(1):27–41

    Article  CAS  PubMed  Google Scholar 

  53. Chen L-L, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12(4):381–388

    Article  PubMed  PubMed Central  Google Scholar 

  54. You X, Vlatkovic I, Babic A et al (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18(4):603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Li J, Lin H, Sun Z et al (2018) High-throughput data of circular RNA profiles in human temporal cortex tissue reveals novel insights into temporal lobe epilepsy. Cell Physiol Biochem 45(2):677–691

    Article  CAS  PubMed  Google Scholar 

  56. Zhao M, Gao F, Zhang D et al (2017) Altered expression of circular RNAs in Moyamoya disease. J Neurol Sci 381:25–31

    Article  CAS  PubMed  Google Scholar 

  57. Wilusz JE, Sharp PA (2013) A circuitous route to noncoding RNA. Science 340(6131):440–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lin S-P, Ye S, Long Y et al (2016) Circular RNA expression alterations are involved in OGD/R-induced neuron injury. Biochem Biophys Res Commun 471(1):52–56

    Article  CAS  PubMed  Google Scholar 

  59. Bensimon G, Ludolph A, Agid Y et al (2008) Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain 132(1):156–171

    Article  PubMed  PubMed Central  Google Scholar 

  60. Prusiner SB, Woerman AL, Mordes DA et al (2015) Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A 112(38):E5308–E5317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McCann H, Stevens CH, Cartwright H et al (2014) α-Synucleinopathy phenotypes. Parkinsonism Relat Disord 20:S62–S67

    Article  PubMed  Google Scholar 

  62. Enuka Y, Lauriola M, Feldman ME et al (2015) 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  PubMed  PubMed Central  Google Scholar 

  63. Chen BJ, Mills JD, Takenaka K et al (2016) Characterization of circular RNAs landscape in multiple system atrophy brain. J Neurochem 139(3):485–496

    Article  CAS  PubMed  Google Scholar 

  64. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Selvaggi L, Loverro G, Schena F et al (1988) Long term follow-up of women with hypertension in pregnancy. Int J Gynaecol Obstet 27(1):45–49

    Article  CAS  PubMed  Google Scholar 

  66. Díaz LM, Díaz MPN, Serrano ND et al (2011) The prognosis for children of mothers with preeclampsia. Part 2: long-term effects. Arch Argent Pediatr 109(6):519–524

    Article  Google Scholar 

  67. Ji L, Brkić J, Liu M et al (2013) Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Asp Med 34(5):981–1023

    Article  CAS  Google Scholar 

  68. Burd CE, Jeck WR, Liu Y et al (2010) Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6(12):e1001233

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

RO is thankful to the Central University of Rajasthan for providing UGC fellowship.

Disclosure Statement

No potential conflict of interest was reported by authors.

Author information

Authors and Affiliations

  1. Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, India

    Rupal Ojha, Raj Nandani, Nina Chatterjee & Vijay Kumar Prajapati

Authors
  1. Rupal Ojha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raj Nandani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nina Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijay Kumar Prajapati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vijay Kumar Prajapati .

Editor information

Editors and Affiliations

  1. School of Life Science, Institute of Cardiovascular Sciences, Shanghai University, Shanghai, China

    Junjie Xiao

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ojha, R., Nandani, R., Chatterjee, N., Prajapati, V.K. (2018). Emerging Role of Circular RNAs as Potential Biomarkers for the Diagnosis of Human Diseases. 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_12

Download citation

Publish with us

Policies and ethics

Search

Navigation