Skip to main content

Advertisement

SpringerLink
Log in

Differential miRNA expression in pleural effusions derived from extracellular vesicles of patients with lung cancer, pulmonary tuberculosis, or pneumonia

  • Original Article
  • Published:
Tumor Biology

Abstract

MicroRNAs (miRNAs) have been found to play important regulatory roles in various physiological and pathological processes. MiRNAs also exhibit high stability and are present at high concentrations in human bodily fluids. Consequently, miRNAs may represent attractive and novel diagnostic biomarkers for certain clinical conditions. Recently, the capacity for extracellular vesicles, including microvesicles and exosomes, to carry miRNAs that participate in cell-to-cell communication has been described. In the present study, the miRNA expression patterns for three kinds of pleural effusions that were obtained from patients with pneumonia (group A), pulmonary tuberculosis (group B), and lung cancer (group C) were detected with high-throughput sequencing. When the expression levels of these miRNAs were compared among the three groups, three differentially expressed miRNAs were detected between groups A and B, while 27 differentially expressed miRNAs were detected between groups A and C. Notably, miR-378i was significantly elevated only in group B, while miR-205-5p and miR-200b were markedly increased only in group C (p < 0.01). Further studies are needed to confirm whether these differentially expressed miRNAs may serve as prospective diagnostic markers for pulmonary diseases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Samir EA, Imre MG, Breakefield XO, Wood MJA. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–57.

    Article  Google Scholar 

  2. Graca R, Willem S. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83.

    Article  Google Scholar 

  3. Yuko O, Yuri M, Akira H, Masami KA, Yoshihiro A, Hayato K, et al. Proteomic analysis of two types of exosomes in human whole saliva. Biol Pharm Bull. 2011;34(1):13–23.

    Article  Google Scholar 

  4. Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004;101(36):13368–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mrvar-Brečko A, Šuštar V, Janša V, Štukelj R, Janša R, Mujagić E, et al. Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope. Blood Cells Mol Dis. 2010;44(4):307–12.

    Article  PubMed  Google Scholar 

  6. Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295–305.

    Article  CAS  PubMed  Google Scholar 

  7. Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, et al. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line lim1863-derived exosomes. Methods (San Diego, Calif). 2012;56(2):293–304.

    Article  CAS  Google Scholar 

  8. Lawson C, Vicencio JM, Yellon DM, Davidson SM. Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J Endocrinol. 2016;228(2):R57–71.

    Article  PubMed  Google Scholar 

  9. Erdbrugger U, Lannigan J. Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry Part A : the journal of the International Society for Analytical Cytology. 2016;89(2):123–34.

    Article  Google Scholar 

  10. Simons M, Raposo G. Exosomes—vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21(4):575–81.

    Article  CAS  PubMed  Google Scholar 

  11. György B, Szabó TG, Pásztói M, Pál Z, Misják P, Aradi B, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cellular & Molecular Life Sciences. 2011;68(16):2667–88.

    Article  Google Scholar 

  12. Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’. Semin Immunopathol. 2011;33(5):455–67.

    Article  PubMed  Google Scholar 

  13. Yi L, Samir EA, Wood MJA. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012;21(21):R125–34.

    Google Scholar 

  14. Yoon YJ, Kim OY, Gho YS. Extracellular vesicles as emerging intercellular communicasomes. BMB Rep. 2014;47(10):531–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Campos JH, Soares RP, Ribeiro K, Andrade AC, Batista WL, Torrecilhas AC. Extracellular vesicles: role in inflammatory responses and potential uses in vaccination in cancer and infectious diseases. Journal of Immunology Research. 2015;2015:832057.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Whiteside TL. Tumour-derived exosomes or microvesicles: another mechanism of tumour escape from the host immune system? Br J Cancer. 2005;92(2):209–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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(6):654–9.

    Article  CAS  PubMed  Google Scholar 

  18. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science (New York, NY). 2001;294(5543):853–8.

    Article  CAS  Google Scholar 

  19. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113(6):673–6.

    Article  CAS  PubMed  Google Scholar 

  20. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCl12-dependent vascular protection. Sci Signal. 2009;2(100):ra81.

    Article  PubMed  Google Scholar 

  21. Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, Gonzalez MA, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chen WX, Liu XM, Lv MM, Chen L, Zhao JH, Zhong SL, et al. Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs. PLoS One. 2014;9(4):e95240.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K, et al. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood. 2013;121(6):984–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Valencia K, Luis-Ravelo D, Bovy N, Anton I, Martinez-Canarias S, Zandueta C, et al. MiRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization. Molecular Oncology. 2014;8(3):689–703.

    Article  CAS  PubMed  Google Scholar 

  25. McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem. 2011;57(6):833–40.

    Article  CAS  PubMed  Google Scholar 

  26. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.

    Article  CAS  PubMed  Google Scholar 

  27. 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(30):10513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc. 1985;60(3):158–64.

    Article  CAS  PubMed  Google Scholar 

  29. Mcgrath EE, Anderson PB. Diagnosis of pleural effusion: a systematic approach. American Journal of Critical Care: an official publication, American Association of Critical-Care Nurses. 2011;20(2):119–28.

    Article  Google Scholar 

  30. Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9(9):513–21.

    Article  CAS  PubMed  Google Scholar 

  31. Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80(2):193–208.

    Article  PubMed  Google Scholar 

  32. Xu J, Zhao J, Evan G, Xiao C, Cheng Y, Xiao J. Circulating microRNAs: novel biomarkers for cardiovascular diseases. Journal of Molecular Medicine (Berlin, Germany). 2012;90(8):865–75.

    Article  CAS  Google Scholar 

  33. Bard MP, Hegmans JP, Annabrita H, Luider TM, Rob W, Severijnen LAA, et al. Proteomic analysis of exosomes isolated from human malignant pleural effusions. American Journal of Respiratory Cell & Molecular Biology. 2004;31(1):114–21.

    Article  CAS  Google Scholar 

  34. Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One. 2014;9(4):e92921.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161–72.

    Article  CAS  PubMed  Google Scholar 

  36. Ji H, Chen M, Greening DW, He W, Rai A, Zhang W, et al. Deep sequencing of RNA from three different extracellular vesicle (EV) subtypes released from the human LIM1863 colon cancer cell line uncovers distinct miRNA-enrichment signatures. PLoS One. 2014;9(10):e110314. doi:10.1371/journal.pone.0110314.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Dweep H, Gretz N. MiRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015;12(8):697.

    Article  CAS  PubMed  Google Scholar 

  40. Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine. 2013;44(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  41. Liu Y, Lu Q. Extracellular vesicle microRNAs: biomarker discovery in various diseases based on RT-qPCR. Biomark Med. 2015;9(8):791–805.

    Article  PubMed  Google Scholar 

  42. Pfeifer P, Werner N, Jansen F. Role and function of microRNAs in extracellular vesicles in cardiovascular biology. Biomed Res Int. 2015;2015:161393.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clinical Lung Cancer. 2009;10(1):42–6.

    Article  CAS  PubMed  Google Scholar 

  44. Wu J, Lu C, Diao N, Zhang S, Wang S, Wang F, et al. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study. Hum Immunol. 2012;73(1):31–7.

    Article  CAS  PubMed  Google Scholar 

  45. Fu Y, Yi Z, Wu X, Li J, Xu F. Circulating microRNAs in patients with active pulmonary tuberculosis. J Clin Microbiol. 2011;49(12):4246–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Maertzdorf J, Weiner 3rd J, Mollenkopf HJ, Bauer T, Prasse A, et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc Natl Acad Sci U S A. 2012;109(20):7853–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X. Modulation of t cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol. 2011;48(9–10):1084–90.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang X, Guo J, Fan S, Li Y, Wei L, Yang X, et al. Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis. PLoS One. 2013;8(12):e81076.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Mazeh H, Mizrahi I, Ilyayev N, Halle D, Brucher B, Bilchik A, et al. The diagnostic and prognostic role of microRNA in colorectal cancer—a comprehensive review. Journal of Cancer. 2013;4(3):281–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bandres E, Agirre X, Ramirez N, Zarate R, Garcia-Foncillas J. MicroRNAs as cancer players: potential clinical and biological effects. DNA Cell Biol. 2007;26(5):273–82.

    Article  CAS  PubMed  Google Scholar 

  51. Xie B, Ding Q, Han H, Wu D. miRCancer: a microRNA-cancer association database constructed by text mining on literature. Bioinformatics (Oxford, England). 2013;29(5):638–44.

    Article  CAS  Google Scholar 

  52. Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119(3):586–93.

    Article  CAS  PubMed  Google Scholar 

  53. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.

    Article  CAS  PubMed  Google Scholar 

  54. Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, et al. MicroRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2013;8(9):1156–62.

    Article  CAS  Google Scholar 

  55. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. Mir-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2011;6(3):482–8.

    Article  Google Scholar 

  56. Mao G, Liu Y, Fang X, Liu Y, Fang L, Lin L, et al. Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer. Angiogenesis. 2015;18(3):373–82.

    Article  CAS  PubMed  Google Scholar 

  57. Jiang M, Zhang P, Hu G, Xiao Z, Xu F, Zhong T, et al. Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients. Mol Cell Biochem. 2013;383(1–2):67–75.

    Article  CAS  PubMed  Google Scholar 

  58. He WJ, Li WH, Jiang B, Wang YF, Xia YX, Wang L. MicroRNAs level as an initial screening method for early-stage lung cancer: a bivariate diagnostic random-effects meta-analysis. Int J Clin Exp Med. 2015;8(8):12317–26.

    PubMed  PubMed Central  Google Scholar 

  59. Halvorsen AR, Bjaanaes M, LeBlanc M, Holm AM, Bolstad N, Rubio L, et al. A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer. Oncotarget. 2016. doi:10.18632/oncotarget.9363.

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81360083), the Youth Innovation Team of the Second Affiliated Hospital of Nanchang University (No. 2016YNTD12002) and Science and Technology Department of Jiangxi Province, China (No. 20143BBM26060).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China

    Jin Lin, Yan Wang, Ye-Qing Zou, Xin Chen, Bo Huang, Jing Liu, Yan-Mei Xu, Jing Zhang, Wei-Ming Yang, Qing-Hua Min, Fan Sun, Shu-Qi Li, Qiu-Fang Gao & Xiao-Zhong Wang

  2. Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Jing Li

Authors
  1. Jin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ye-Qing Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan-Mei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei-Ming Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qing-Hua Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Fan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Shu-Qi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Qiu-Fang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Xiao-Zhong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao-Zhong Wang.

Ethics declarations

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University, China. All of the participating patients provided a signed informed consent.

Conflicts of interest

None.

Additional information

Jin Lin, Yan Wang, and Ye-Qing Zou contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, J., Wang, Y., Zou, YQ. et al. Differential miRNA expression in pleural effusions derived from extracellular vesicles of patients with lung cancer, pulmonary tuberculosis, or pneumonia. Tumor Biol. 37, 15835–15845 (2016). https://doi.org/10.1007/s13277-016-5410-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5410-6

Keywords

Search

Navigation